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Biomedical subjects

H Burton

Publications and source records attributed to H Burton.

At least 19 recordsLinked to original sources

Tracking neuronal fiber pathways in the living human brain.

Functional imaging with positron emission tomography and functional MRI has revolutionized studies of the human brain. Understanding the organization of brain systems, especially those used for cognition, remains limited, however, because no methods currently exist for noninvasive tracking of neuronal connections between functional regions [Crick, F. & Jones, E. (1993) Nature (London) 361, 109-110]. Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.

Brain

Anatomical evidence for the posterior boundary of area 2 in the macaque monkey.

This study examined the architectonic organization of the macaque's primary somatosensory cortex near the tip of the intraparietal sulcus (IPS), using myelin and Nissl stains plus immunohistochemical labeling with the SMI-32 antibody. The surface cortex between the IPS and central sulcus (overlapping area 2) was distinguished from surrounding cortex (areas 1 post-central dimple and cortex immediately anterior to the tip of the IPS. Physiological mappings verified that the and 5) by relatively light SMI-32 immunoreactivity. This distinguishing architectonic feature was most evident between the architectonic transition correlated with a change in receptive field properties, consistent with their marking the boundary between areas 2 and 5. These results suggest that area 2 occupies surface cortex anterior to the IPS, but not within the IPS.

Animals

Vibrotactile stimulus order effects in somatosensory cortical areas of rhesus monkeys.

This study demonstrated effects of stimulus order on single-cell responses in the macaque primary and secondary somatosensory and 7b cortical areas. As part of a study of tactile attention, two monkeys (Macaca mulatta) received similar constant amplitude, sinusoidal tactile vibration patterns (125 Hz) at two glabrous skin, hand locations. The stimuli started asynchronously with offsets of 150 or 300 ms. In cells with bilateral receptive fields and increased firing to a stimulus, we observed an average lowering of 30% in the firing rates to the contralateral stimulus when preceded by stimulation of the ipsilateral hand. Some cells with only contralateral receptive fields showed similar depressed responses to a contralateral stimulus when preceded by an ipsilateral stimulus. Stimulus order effects were more prominent during dual stimulation of the receptive field on one hand. In six cells whose background activity was inhibited by the first stimulus, higher rates appeared at the onset of the second stimulus. These results suggest a possible substrate for psychophysical findings of stimulus masking in which a preceding stimulus depresses detection thresholds. The spatial and temporal characteristics of in-field inhibitory mechanisms best account for the observed stimulus order effects.

Animals

Tactile-spatial and cross-modal attention effects in the second somatosensory and 7b cortical areas of rhesus monkeys.

This study analyzed neuronal responses in the second somatosensory (SII) and 7b cortical areas during a selective attention task. Cues directed attention to one of three simultaneous stimuli: vibrotactile stimuli applied to mirror sites on both hands or to a similarly timed auditory tone. Two stimulus patterns appeared with equal probability for the cued stimulus: a constant amplitude sinewave or the latter with a superimposed brief amplitude pulse midway in the trial. Uncued stimuli always contained amplitude pulses. Monkeys demonstrated whether an amplitude pulse at the cued location was present or absent by making appropriately rewarded up and down foot pedal movements. Cue location and stimulus pattern varied trial-wise and pseudo-randomly. Average firing rates to vibrotactile stimuli in 82 of 181 SII cells and 13 of 22 area 7b cells differed significantly during at least one epoch for trials cued to the contralateral hand when compared to trials cued to the ipsilateral hand or auditory stimulus. Predominant were relatively suppressed firing rates during times prior to the epoch containing the amplitude pulses or enhanced activity during and after these pulses. Generally, different cells showed suppression early vs enhancement later in a trial. Analyses of the ratio between firing rates before and during the amplitude pulses suggested improved evoked signals to the amplitude pulses. The discussion considers attention as a mechanism for reducing distractions, early in the trial through suppressing these signals, or for selectively increasing response magnitudes in the cued channel, especially around times when amplitude pulses were present or absent.

Acoustic Stimulation

Chemical restraint of southern elephant seals (Mirounga Leonina); use of medetomidine, ketamine and atipamezole and comparison with other cyclohexamine-based combinations.

A study was conducted to assess the effectiveness of the alpha-2 agonist medetomidine for sedation of pre-moulting, mature female southern elephant seals (Mirounga leonina). Two animals were sedated with a single intramuscular dose of medetomidine (0.013 and 0.027 mg kg-1). A further two groups of five animals received medetomidine (0.017 mg kg-1) combined with ketamine (1.90 mg kg-1) and, 20 min later, either saline or the alpha-2 antagonist atipamezole (0.04 mg kg-1) intravenously. Medetomidine alone did not give sufficient restraint to permit intravenous access. The response appeared to be similar to previous findings with ketamine and xylazine. Administration of atipamezole had little effect upon the level and timecourse of restraint. Ketamine and medetomidine seem to offer few advantages over ketamine and xylazine or other cyclohexamine-drug combinations for routine chemical restraint of southern elephant seals.

Anesthetics, Dissociative

Responses in primary somatosensory cortex of rhesus monkey to controlled application of embossed grating and bar patterns.

Responses of 66 neurons in primary somatosensory cortex (SI) of three anesthetized monkeys (Macaca mulatta) were characterized with grating patterns of 550- to 2900-mm groove width (Gw) and 250-mm ridge width, and/or pairs of 3-mm-wide ridges (bars) spaced 1-20 mm apart. Surfaces were stroked across single fingertips at parametrically varied levels of force (25-150 g) and velocity (25-100 mm/sec). The average firing rates (AFRs) of many cells varied with Gw, but force and velocity altered response functions (e.g., from linear to plateau or inverted). Slowly adapting (SA) cells were more sensitive to force, rapidly adapting (RA) cells to velocity. Force and velocity affected all cells sensitive to Gw, which suggests that response independence (e.g., AFR correlated with Gw but not force or velocity) may require active touch. Discharge intervals of many cells replicated stimulus temporal period. This temporal fidelity in SAs far exceeded examples reported for active touch. However, discharge burst duration and AFR increased with Gw, supporting a neural rate rather than temporal code for roughness. Force and velocity altered the Gw at which some cells fired once in phase to stimulus cycle ("tuning point"). Responses to bar edges suggest cortical replication of peripheral mechanoreceptor sensitivity to skin curvature, leading to this temporal fidelity in some cortical cells. Graded RA responses to Gw without obvious stimulus temporal replication may reflect early stages of integrative processing in supra- and infragranular layers that blur obvious temporal patterning and lead to a rate code correlated with spatial variation and proportional to perceived roughness.

Afferent Pathways

Discrimination of vibrotactile frequencies in a delayed pair comparison task.

This study quantified human short-term-memory decay functions for delayed vibrotactile frequency discriminations. Subjects indicated which of two successive intervals contained the higher or lower frequency of a pair separated by delay periods of 0.5-30 sec. Performance decreased as a function of length of delay and was higher when delays were unfilled than when they were filled with a backwards-counting task. This interpolated task may have interfered with rehearsal of a coded representation of the remembered vibrotactile frequency. A change in decay rate after 5-sec delays suggests a switch from reliance on sensory memory to the coded frequency representation. Performance and decay rate depended on presentation order of higher or lower frequency within pairs. Reciprocal performance asymmetries seen in high-versus low-frequency ranges did not result from simple response bias.

Adult

Ipsilateral intracortical connections of physiologically defined cutaneous representations in areas 3b and 1 of macaque monkeys: projections in the vicinity of the central sulcus.

This study examined cortical connections of areas 3b and 1 in 17 macaque monkeys in reference to regional somatotopography. The fluorescent retrograde tracers Fast Blue and Diamidino Yellow and the anterograde tracer Rhodamine Dextran were injected into closely related cutaneously responsive sites in primary somatosensory cortex, e.g., adjacent digits. Supra- and infragranular layers in nearly all studied areas contained labeled pyramidal cells. Labeled infragranular cells predominated at the fringes of a distribution where cells labeled from different tracer injections in the same brain intermixed more. All topographical regions across area 1 have reciprocal connections with areas 4, 3a, 3b, 1, 2, and 5. Intrinsic connections within area 1 and between it and area 2 are greatest; those with area 3b are less. Intrinsic connections within area 3b exceed all other nearby projections from this area which reciprocally connects with areas 3a, 1 and 2. Connections appear topographically organized, including those with poorly mapped regions, like area 5. These connections link representations of neighboring skin and skip map regions that include disjoint dermatomal areas. Connections from adjacent digit representations overlap; however, double-labeled cells were not found. Distal and proximal digit zones mostly interconnect within an area. Intrinsic connections spread further in area 1 than in area 3b, thereby joining more disparate topographical zones than interareal connections, which project more homotopically. The domain over which the map in somatosensory cortical area I (SI) dynamically changes following intracortical microstimulation (Recanzone, Merzenich and Dinse, Cerebral Cortex 2:181-196, 1992) may depend on the range of intrinsic connections observed in this study. The extent of connections between cortical areas was less than expected and this challenges the hypothesis that these connections directly create receptive field enlargements.

Animals

Cortical areas within the lateral sulcus connected to cutaneous representations in areas 3b and 1: a revised interpretation of the second somatosensory area in macaque monkeys.

Cortical connections between various body representations in areas 3b and 1 and lateral parietal cortex were examined in 18 macaque monkeys. We injected tracers (Fast Blue, Diamidino Yellow, Horseradish Peroxidase, and Rhodamine Dextran), alone or in combination, into closely related cutaneous responsive sites, e.g., adjacent digits. Separated patches of labeling were found across the parietal operculum and insula for all injected locations. On the basis of cytoarchitectural criteria, the labeled regions include the second somatosensory area (SII), retroinsular area (Ri) and granular insula (Ig). Assuming the connections are homotopical from physiologically identified body representations in primary somatosensory cortex, the labeling patterns in SII include complete anterior and posterior body maps. The orientation of the body is erect in the posterior and supine in the anterior SII region. Area 3b has greater density of connections with anterior SII. The maps are mirror images aligned along the distal extremities. The anterior-posterior (A-P) length of the "SII region" exceeds 7 mm; it extends in the coronal plane from the fundus of the lateral sulcus to surface cortex near the anterior tip of the intraparietal sulcus. Two additional topographically organized maps are likely in Ri. These are "worm-like" body maps oriented along the A-P axis and joined at the head representation. Connections with the center of Ig are not somatotopically organized. The diversity of somatosensory areas in lateral parietal cortex revealed by the labeled connections was discussed in reference to prior mapping of SII in monkeys and was compared to reports of multiple areas in this region of cortex in other species.

Animals

Blood flow changes in human somatosensory cortex during anticipated stimulation.

Positron emission tomography (PET) measurements of brain blood flow were used to monitor changes in the human primary and secondary somatosensory cortices during the period when somatosensory stimuli were expected. In anticipation of either focal or innocuous touching, or localized, painful shocks, blood flow decreased in parts of the primary somatosensory cortex map located outside the representation of the skin area that was the target of the expected stimulus. Specifically, attending to an impending stimulus to the fingers produced a significant decrease in blood flow in the somatosensory zones for the face, whereas attending to stimulation of the toe produced decreases in the zones for the fingers and face. Decreases were more prominent in the side ipsilateral to the location of the expected stimulus. No significant changes in blood flow occurred in the region of the cortex representing the skin locus of the awaited stimulation. These results are concurrent with a model of spatial attention in which potential signal enhancement may rely on generalized suppression of background activity.

Adult

Antagonism of some cyclohexamine-based drug combinations used for chemical restraint of southern elephant seals (Mirounga leonina).

This study examined the use of 4 antagonists of chemical restraint in mature female southern elephant seals (Mirounga leonina) that were restrained with ketamine and diazepam, ketamine and xylazine, or tiletamine and zolazepam. The antagonists were: 4-aminopyridine, yohimbine, doxapram and sarmazenil. The effects of the antagonists on the animal's time to first movement forward and recovery, heart rate, respiratory rate and venous blood gas and pH values, and level of chemical restraint were recorded. Sarmazenil (1.0 mg/kg) and doxapram (5.0 mg/kg) partially antagonised 50:1 ketamine: diazepam (ketamine = 3.0 mg/kg, diazepam = 0.06 mg/kg) and tiletamine and zolazepam (tiletamine = 0.5 mg/kg, zolazepam = 0.5 mg/kg). However, the rapid recovery after low doses of anaesthetics means that antagonism is usually unnecessary, and it may increase the likelihood of shaking. Routine antagonism of ketamine and xylazine (ketamine = 3.0 mg/kg, xylazine = 0.5 mg/kg) is more useful given its usually delayed recovery time and potential for thermoregulatory problems. For this purpose yohimbine (0.06 mg/kg) offered advantages over doxapram in giving a smoother recovery with less aggression. 4-aminopyridine (0.2 mg/kg) prolonged chemical restraint by 100:1 ketamine:diazepam (ketamine = 3.0 mg/kg, diazepam = 0.03 mg/kg) and ketamine and xylazine, and should be contraindicated. Doxapram (5.0 mg/kg) was the most useful general antagonist for all groups of drugs but shaking was seen and a lower dose is recommended.

4-Aminopyridine

Use of midazolam, pethidine, ketamine and thiopentone for the restraint of southern elephant seals (Mirounga leonina).

Thirty-two pre-moulting female southern elephant seals (Mirounga leonina) were heavily sedated with midazolam (0.04 mg/kg) combined with pethidine (4 mg/kg). This combination made it possible to give the seals intravenous injections and was rapidly antagonised by naloxone. After sedation with midazolam and pethidine, 2 to 3 mg/kg intravenous thiopentone or ketamine induced light immobilisation for approximately five minutes and allowed the animals to be intubated. Prolonged deep levels of restraint were achieved after sedation with midazolam and pethidine by repeated intravenous doses of approximately 1.5 mg ketamine/kg at 10 minute intervals, to maintain restraint for 60 minutes.

Animals

Representation of tactile roughness in thalamus and somatosensory cortex.

Neuronal responses were recorded in the thalamic ventroposterior lateral nucleus and primary and secondary somatosensory cortical areas of two rhesus monkeys performing a tactile discrimination task. The subjects actively stroked their fingertips over gratings that varied in groove width. Many cells in each location displayed average firing rates that incrementally reflected groove with dimensions (0.5-2.9 mm). Approximately 10% of cortical cells were more active to surfaces with narrower grooves. i.e., had negative graded response functions. All thalamic cells and approximately 50% of cortical cells with positive graded functions to gratings also showed increased responsiveness to contact force. Some cells also varied their activity with stroke speed. Many thalamic, a few primary somatosensory cortical cells, and no secondary somatosensory cortical cells showed periodic firing patterns that reflected the spatial-temporal frequency of stimulation. Responses to gratings of nearly every cell with negative graded responses and the remaining cortical cells with positive functions were independent of contact force and stroke velocity. The results only partially confirm predictions based on different models of texture perception that propose spatial, intensive, or cross modal neural codes. Negative graded response functions may require a form of spatial convergence across a cell's receptive field that has not previously been discussed by these models.

Animals

Neuronal activity in the second somatosensory cortex of monkeys (Macaca mulatta) during active touch of gratings.

1. In penetrations made into the upper bank of the lateral sulcus in two monkeys (Macaca mulatta), cells were isolated from the second somatosensory cortex (SII). During single-cell recordings, animals performed an active touch task in which they rubbed their fingertips over pairs of gratings differing in groove width and indicated which was the smoother surface. Hand motion and downward applied force were measured and recorded during these strokes. 2. In this survey, 151 penetrations provided observations on 352 cells that responded to passive stimulation of the digits or during performance of the active touch task. Consistent with previous reports, receptive fields (RFs) in SII were large, often multi-digit, and frequently included a portion or all of the hand and occasionally the arm. Modality was determined for 92 of 127 fully characterized cells, and included 70 cutaneous, 5 deep, 11 Pacinian corpuscle, and 6 joint cells. Characteristic of SII, modality could not be defined in 35 cells that were unresponsive to passive stimulation or whose responses varied widely over time. 3. Response properties of a subgroup of 79 cells in SII resembled those previously studied in the primary somatosensory cortex (SI) and ventroposterior lateral nucleus of the thalamus (VPL) using identical procedures. Correlation analysis revealed that 29 of these cells, like a portion of cells in SI, responded to changes in groove width independent of force or velocity. This selectivity could be considered a form of feature specificity. 4. In contrast to SI and VPL, transient responses to the fingertips contacting small elevated metal bars, which demarcated the beginning, middle, and end of strokes across the gratings, were seen in a majority of SII cells (109/127). During contact with bars, 89 cells displayed excitatory responses and 20 cells showed suppressed activity. Twelve cells, which responded to bars in isolation from gratings, provided a possible example of increased stimulus selectivity. 5. Passive stimulation failed to activate 16 cells that responded, in some cases differentially to gratings or force, during the task. Responses of nine other cells demonstrated task-dependent modulation in the form of response reduction or enhancement during selected portions of the stroke. In these same cells, response changes did not occur under comparable stimulus conditions in other portions of the stroke that differed only in behavioral context. These types of selective response modulations, not noted in our previous studies of VPL or SI, suggest that mechanisms regulating sensory inputs may affect SII.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways

Tactile-vibration-activated foci in insular and parietal-opercular cortex studied with positron emission tomography: mapping the second somatosensory area in humans.

Positron emission tomographic measurements were used to study the distribution of focal changes in cerebral blood flow (CBF) induced by vibrotactile stimulation of the hands and feet in 22 normal humans. Subjects received bolus intravenous saline injections containing approximately 60 mCi 15O-labeled water. Active regions during stimulation were defined relative to resting, nonstimulated states. Scan data from different subjects were averaged after stereotactic standardization. The results identified previously described foci of increased CBF in postrolandic sensory cortex (primary somatosensory cortex) and supplementary motor cortex. New statistical testing procedures provided independent demonstrations of two additional increases in regional CBF, bilaterally, within the sylvian fissure. One site along the parietal operculum corresponded to previous conjectures about a second somatosensory cortical area (SII) in humans. Another site also was found on the insula. No topographic organization was found in either location. The discussion considers these responsive areas to innocuous tactile stimuli in reference to suggestions about a role for SII in the perception of pain.

Adult

Ipsilateral cortical connections of primary somatic sensory cortex in rats.

The organization of ipsilateral cortical connections of the rat primary somatic sensory area (SI) was analyzed following small injections of multiple fluorescent tracers in the same case, into two or three SI body representations identified electrophysiologically. Labeling patterns were studied in tangential cortical sections and in flattened reconstructions from coronal sections. The cytochrome oxidase staining in tangential sections served as a control for injection location and to position labeling patterns found within granular portion of SI. The results show that most connections made with SI are reciprocal. Their topographical organization show different degrees of precision in the different areas. Homotypical and heterotypical connections were defined, the latter being more evident within the granular portion of SI. The findings: (1) were consistent with subdividing rat SI into four distinct areas with each having its own pattern of connections, (2) revealed two topographically organized regions in parietal cortex lateral to SI called second somatosensory (SII) and parietal ventral (PV) areas, (3) confirmed a topographical pattern in motor cortex and suggested an organization for connections between SI and an agranular medial field, and (4) demonstrated three more regions in parietal cortex connected to SI: posterior to SI called parietal medial; lateral to PV called parietal rhinal; posterior to SII called parietal lateral. Differences were noted in the distinctions between and within the maps when label distributions were plotted separately from supra- and infragranular layers. These findings agree with previous parcellations of the rat SI (Chapin et al., '87: J. Comp Neurol 263:326-346), squirrel PV and SII (Krubitzer et al., '86: J. Comp Neurol 250:403-430), and the organization of rat corticospinal neurons in many of the same areas (Li et al., '90: Somat Motor Res 7:315-335).

Animals