Mark J. Burish

Functional Trade-Offs in White Matter Axonal Scaling

The brains of large mammals have lower rates of metabolism than those of small mammals, but the functional consequences of this scaling are not well understood. An attractive target for analysis is axons, whose size, speed and energy consumption are straightforwardly related. Here we show that from shrews to whales, the composition of white matter shifts from compact, slow-conducting, and energetically expensive unmyelinated axons to large, fast-conducting, and energetically inexpensive myelinated axons. The fastest axons have conduction times of 1–5 ms across the neocortex and <1 ms from the eye to the brain, suggesting that in select sets of communicating fibers, large brains reduce transmission delays and metabolic firing costs at the expense of increased volume. Delays and potential imprecision in cross-brain conduction times are especially great in unmyelinated axons, which may transmit information via firing rate rather than precise spike timing. In neocortex, axon size distributions can account for the scaling of per-volume metabolic rate and suggest a maximum supportable firing rate, averaged across all axons, of 7 ± 2 Hz. Axon size distributions also account for the scaling of white matter volume with respect to brain size. The heterogeneous white matter composition found in large brains thus reflects a metabolically constrained trade-off that reduces both volume and conduction time.

Cortical and subcortical plasticity in the brains of humans, primates, and rats after damage to sensory afferents in the dorsal columns of the spinal cord.

The failure of injured axons to regenerate following spinal cord injury deprives brain neurons of their normal sources of activation. These injuries also result in the reorganization of affected areas of the central nervous system that is thought to drive both the ensuing recovery of function and the formation of maladaptive neuronal circuitry. Better understanding of the physiological consequences of novel synaptic connections produced by injury and the mechanisms that control their formation are important to the development of new successful strategies for the treatment of patients with spinal cord injuries. Here we discuss the anatomical, physiological and behavioral changes that take place in response to injury-induced plasticity after damage to the dorsal column pathway in rats and monkeys. Complete section of the dorsal columns of the spinal cord at a high cervical level in monkeys and rats interrupts the ascending axon branches of low threshold mechanoreceptor afferents subserving the forelimb and the rest of the lower body. Such lesions render the corresponding part of the somatotopic representation of primary somatosensory cortex totally unresponsive to tactile stimuli. There are also behavioral consequences of the sensory loss, including an impaired use of the hand/forelimb in manipulating small objects. In monkeys, if some of the afferents from the hand remain intact after dorsal column lesions, these remaining afferents extensively reactivate portions of somatosensory cortex formerly representing the hand. This functional reorganization develops over a postoperative period of 1 month, during which hand use rapidly improves. These recoveries appear to be mediated, at least in part, by the sprouting of preserved afferents within the cuneate nucleus of the dorsal column-trigeminal complex. In rats, such functional collateral sprouting has been promoted by the post-lesion digestion of the perineuronal net in the cuneate nucleus. Thus, this and other therapeutic strategies have the potential of enhancing sensorimotor recoveries after spinal cord injuries in humans.

Brain Architecture and Social Complexity in Modern and Ancient Birds

Vertebrate brains vary tremendously in size, but differences in form are more subtle. To bring out functional contrasts that are independent of absolute size, we have normalized brain component sizes to whole brain volume. The set of such volume fractions is the cerebrotype of a species. Using this approach in mammals we previously identified specific associations between cerebrotype and behavioral specializations. Among primates, cerebrotypes are linked principally to enlargement of the cerebral cortex and are associated with increases in the complexity of social structure. Here we extend this analysis to include a second major vertebrate group, the birds. In birds the telencephalic volume fraction is strongly correlated with social complexity. This correlation accounts for almost half of the observed variation in telencephalic size, more than any other behavioral specialization examined, including the ability to learn song. A prominent exception to this pattern is owls, which are not social but still have very large forebrains. Interpolating the overall correlation for Archaeopteryx, an ancient bird, suggests that its social complexity was likely to have been on a par with modern domesticated chickens. Telencephalic volume fraction outperforms residuals-based measures of brain size at separating birds by social structure. Telencephalic volume fraction may be an anatomical substrate for social complexity, and perhaps cognitive ability, that can be generalized across a range of vertebrate brains, including dinosaurs.

Thalamocortical Connections of Functional Zones in Posterior Parietal Cortex and Frontal Cortex Motor Regions in New World Monkeys

Posterior parietal cortex (PPC) links primate visual and motor systems and is central to visually guided action. Relating the anatomical connections of PPC to its neurophysiological functions may elucidate the organization of the parietal-frontal network. In owl and squirrel monkeys, long-duration electrical stimulation distinguished several functional zones within the PPC and motor/premotor cortex (M1/PM). Multijoint forelimb movements reminiscent of reach, defense, and grasp behaviors characterized each functional zone. In PPC, functional zones were organized parallel to the lateral sulcus. Thalamocortical connections of PPC and M1/PM zones were investigated with retrograde tracers. After several days of tracer transport, brains were processed, and labeled cells in thalamic nuclei were plotted. All PPC zones received dense inputs from the lateral posterior nucleus and the anterior pulvinar. PPC zones received additional projections from ventral lateral (VL) divisions of motor thalamus, which were also the primary source of input to M1/PM. Projections to PPC from rostral motor thalamus were sparse. Dense projections from ventral posterior (VP) nucleus of somatosensory thalamus distinguished the rostrolateral grasp zone from the other PPC zones. PPC connections with VL and VP provide links to cerebellar nuclei and the somatosensory system, respectively, that may integrate PPC functions with M1/PM.

Microstimulation and architectonics of frontoparietal cortex in common marmosets (Callithrix jacchus).

We investigated the organization of frontoparietal cortex in the common marmoset (Callithrix jacchus) by using intracortical microstimulation and an architectonic analysis. Primary motor cortex (M1) was identified as an area that evoked visible movements at low levels of electric current and had a full body representation of the contralateral musculature. Primary motor cortex represented the contralateral body from hindlimb to face in a mediolateral sequence, with individual movements such as jaw and wrist represented in multiple nearby locations. Primary motor cortex was coextensive with an agranular area of cortex marked by a distinct layer V of large pyramidal cells that gradually decreased in size toward the rostral portion of the area and was more homogenous in appearance than other New World primates. In addition to M1, stimulation also evoked movements from several other areas of frontoparietal cortex. Caudal to primary motor cortex, area 3a was identified as a thin strip of cortex where movements could be evoked at thresholds similar to those in M1. Rostral to primary motor cortex, supplementary motor cortex and premotor areas responded to higher stimulation currents and had smaller layer V pyramidal cells. Other areas evoking movements included primary somatosensory cortex (area 3b), two lateral somatosensory areas (areas PV and S2), and a caudal somatosensory area. Our results suggest that frontoparietal cortex in marmosets is organized in a similar fashion to that of other New World primates. J. Comp. Neurol. 507:1151–1168, 2008.

Widespread spatial integration in primary somatosensory cortex

Tactile discrimination depends on integration of information from the discrete receptive fields (RFs) of peripheral sensory afferents. Because this information is processed over a hierarchy of subcortical nuclei and cortical areas, the integration likely occurs at multiple levels. The current study presents results indicating that neurons across most of the extent of the hand representation in monkey primary somatosensory cortex (area 3b) interact, even when these neurons have separate RFs. We obtained simultaneous recordings by using a 100-electrode array implanted in the hand representation of primary somatosensory cortex of two anesthetized owl monkeys. During a series of 0.5-s skin indentations with single or dual probes, the distance between electrodes from which neurons with synchronized spike times were recorded exceeded 2 mm. The results provide evidence that stimuli on different parts of the hand influence the degree of synchronous firing among a large population of neurons. Because spike synchrony potentiates the activation of commonly targeted neurons, synchronous neural activity in primary somatosensory cortex can contribute to discrimination of complex tactile stimuli.

Chondroitinase ABC promotes selective reactivation of somatosensory cortex in squirrel monkeys after a cervical dorsal column lesion

After large but incomplete lesions of ascending dorsal column afferents in the cervical spinal cord, the hand representation in the contralateral primary somatosensory cortex (area 3b) of monkeys is largely or completely unresponsive to touch on the hand. However, after weeks of spontaneous recovery, considerable reactivation of the hand territory in area 3b can occur. Because the reactivation process likely depends on the sprouting of remaining axons from the hand in the cuneate nucleus of the lower brainstem, we sought to influence cortical reactivation by treating the cuneate nucleus with an enzyme, chondroitinase ABC, that digests perineuronal nets, promoting axon sprouting. Dorsal column lesions were placed at a spinal cord level (C5/C6) that allowed a portion of ascending afferents from digit 1 to survive in squirrel monkeys. After 11–12 wk of recovery, the contralateral forelimb cortex was reactivated by stimulating digit 1 more extensively in treated monkeys than in control monkeys. The results are consistent with the proposal that the treatment enhances the sprouting of digit 1 afferents in the cuneate nucleus and that this sprouting allowed these preserved inputs to activate cortex more effectively.

Cellular Scaling Rules for Primate Spinal Cords

The spinal cord can be considered a major sensorimotor interface between the body and the brain. How does the spinal cord scale with body and brain mass, and how are its numbers of neurons related to the number of neurons in the brain across species of different body and brain sizes? Here we determine the cellular composition of the spinal cord in eight primate species and find that its number of neurons varies as a linear function of cord length, and accompanies body mass raised to an exponent close to 1/3. This relationship suggests that the extension, mass and number of neurons that compose the spinal cord are related to body length, rather than to body mass or surface. Moreover, we show that although brain mass increases linearly with cord mass, the number of neurons in the brain increases with the number of neurons in the spinal cord raised to the power of 1.7. This faster addition of neurons to the brain than to the spinal cord is consistent with current views on how larger brains add complexity to the processing of environmental and somatic information.

Response Properties of Neurons in Primary Somatosensory Cortex of Owl Monkeys Reflect Widespread Spatiotemporal Integration

Receptive fields of neurons in somatosensory area 3b of monkeys are typically described as restricted to part of a single digit or palm pad. However, such neurons are likely involved in integrating stimulus information from across the hand. To evaluate this possibility, we recorded from area 3b neurons in anesthetized owl monkeys with 100-electrode arrays, stimulating two hand locations with electromechanical probes simultaneously or asynchronously. Response magnitudes and latencies of single- and multiunits varied with stimulus conditions, and multiunit responses were similar to single-unit responses. The mean peak firing rate for single neurons stimulated within the preferred location was estimated to be ∼26 spike/s. Simultaneous stimulation with a second probe outside the preferred location slightly decreased peak firing rates to ∼22 spike/s. When the nonpreferred stimulus preceded the preferred stimulus by 10-500 ms, peak firing rates were suppressed with greatest suppression when the nonpreferred stimulus preceded by 30 ms (∼7 spike/s). The mean latency for single neurons stimulated within the preferred location was ∼23 ms, and latency was little affected by simultaneous paired stimulation. However, when the nonpreferred stimulus preceded the preferred stimulus by 10 ms, latencies shortened to ∼16 ms. Response suppression occurred even when stimuli were separated by long distances (nonadjacent digits) or long times (500 ms onset asynchrony). Facilitation, though rare, occurred most often when the stimulus onsets were within 0-30 ms of each other. These findings quantify spatiotemporal interactions and support the hypothesis that area 3b is involved in widespread stimulus integration.

Effects of muscimol inactivations of functional domains in motor, premotor, and posterior parietal cortex on complex movements evoked by electrical stimulation

Parietal and frontal cortex are central to controlling forelimb movements. We previously showed that movements such as reach, grasp, and defense can be evoked from primary motor (M1), premotor (PMC), and posterior parietal (PPC) cortex when 500-ms trains of electrical pulses are delivered via microelectrodes. Stimulation sites that evoked a specific movement clustered into domains, which shared a topographic pattern in New World monkeys and prosimian galagos. Matched functional domains in parietal and frontal cortex were preferentially interconnected. We reasoned that matched functional domains form parallel networks involved in specific movements. To test the roles of domains in M1, PMC, and PPC, we systematically inactivated with muscimol domains in one region and determined if functional changes occurred in matching domains in other regions. The most common changes were higher current thresholds for stimulation-evoked movements and shorter, not fully developed, trajectories of movements. Inactivations of an M1 functional domain greatly reduced or abolished movements evoked from the matching domains in PMC or PPC, whereas movements evoked from nonmatching domains remained mostly unaffected. In contrast, inactivating PMC or PPC domains did not consistently abolish the ability to evoke movements from matching M1 domains. However, inactivation of PMC domains suppressed or altered the movements evoked from PPC domains. Thus movement sequences evoked from PMC depend on M1 and movement sequences evoked from PPC depend on both M1 and PMC. Overall, the results support the conclusion that PPC, PMC, and M1 are subdivided into functional domains that are hierarchically related within parallel networks.