R. Jarrett Rushmore

Functional circuitry underlying natural and interventional cancellation of visual neglect

A large body of work demonstrates that lesions at multiple levels of the visual system induce neglect of stimuli in the contralesional visual field and that the neglect dissipates as neural compensations naturally emerge. Other studies show that interventional manipulations of cerebral cortex, superior colliculus or deep-lying midbrain structures have the power to attenuate, or cancel, the neglect and reinstate orienting into a neglected hemifield, and even into a profound cortically blind field. These results, and those derived from experiments on the behavioral impacts of unilateral and bilateral lesions, lead us to evaluate the repercussions of unilateral and bilateral deactivations, neural compensations and cancellations of attentional deficits in terms of an overarching hypothesis of neglect. The cancellations can be both striking and enduring, and they suggest that therapeutic strategies can be developed to reverse or ameliorate neglect in human patients. Animal studies show that in many instances of neglect adequate representations and the accompanying motor mechanisms are present despite the lesion and they simply need to be unmasked and brought into use to effect a remedy.

Functional impact of primary visual cortex deactivation on subcortical target structures in the thalamus and midbrain.

The functional relationships between the primary visual cortex and its major subcortical target structures have long been a subject of interest. We studied these relationships by using localized cooling deactivation to silence portions of primary visual cortex and measuring 2‐deoxyglucose (2DG) uptake to assess neural activity in subcortical and midbrain targets. We focused analysis on the largest subcortical targets of primary visual cortex: the superior colliculus (SC), the dorsal lateral geniculate nucleus of the thalamus (dLGN), and the lateral division of the lateral posterior nucleus of the thalamus (LPL). We found that localized cooling of different regions of primary visual cortex caused specific decreases in 2DG uptake in target structures such that the location of 2DG decrease varied according to joint retinotopy, and the magnitude of the decreases in target structures was associated with the amount of cooled cortex. In addition, we found that the impact of cortical cooling was more profound on the SC than on the dLGN. The functional impact of cortical deactivations on the LPL was weak for small deactivations but approximated the impact on the SC when deactivations were large. We discuss these findings in terms of neural circuits and in terms of drivers and modulators. J. Comp. Neurol. 488:414–426, 2005.

Bilateral impact of unilateral visual cortex lesions on the superior colliculus.

We examined the functional impact of a long-standing, unilateral primary visual cortex lesion on the superior colliculus (SC) using radiolabeled 2-deoxyglucose (2DG) as a marker of neural activity. In accord with known corticotectal connectivity and functional influence, 2DG uptake in the superficial layers of the ipsilesional SC was decreased. We also found a decrease in the superficial layers of the contralesional SC. These data suggest that modifications in activity in one SC can have a substantial influence on activity in its contralateral partner, and that processing in one visual hemifield does not occur independently of processing of signals in the opposite hemifield. The effects are not mediated by the contralateral hemisphere but are probably mediated by intercollicular circuitry.

Neuroplasticity after unilateral visual cortex damage in the newborn cat

Anatomical, electrophysiological, and behavioral studies implicate extrastriate cortex as a major contributor to the sparing of visually guided behaviors following lesions of primary visual cortex incurred early in life. Here we report considerable sparing of the ability to detect and localize stimuli in the hemifield contralateral to unilateral early lesions of all contiguous visually-responsive primary and extrastriate cortical regions (occipital, visuoparietal, and visuotemporal cortices). In the adult cat this same lesion induces a dense blindness and cats are unable to orient to any visual stimulus introduced into the contralesional hemifield. In the absence of cortical circuits, the neural sparing identified following the neonatal lesion is based on the superior colliculus and it occurs despite massive retrograde transynaptic degeneration of large numbers of retinal ganglion cells.

Motor Cortex Neurostimulation Technologies for Chronic Post-stroke Pain: Implications of Tissue Damage on Stimulation Currents

Background: Central post stroke pain (CPSP) is a highly refractory syndrome that can occur after stroke. Primary motor cortex (M1) brain stimulation using epidural brain stimulation (EBS), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS) have been explored as potential therapies for CPSP. These techniques have demonstrated variable clinical efficacy. It is hypothesized that changes in the stimulating currents that are caused by stroke-induced changes in brain tissue conductivity limit the efficacy of these techniques. Methods: We generated MRI-guided finite element models of the current density distributions in the human head and brain with and without chronic focal cortical infarctions during EBS, TMS, and tDCS. We studied the change in the stimulating current density distributions’ magnitude, orientation, and maxima locations between the different models. Results: Changes in electrical properties at stroke boundaries altered the distribution of stimulation currents in magnitude, location, and orientation. Current density magnitude alterations were larger for the non-invasive techniques (i.e., tDCS and TMS) than for EBS. Nonetheless, the lesion also altered currents during EBS. The spatial shift of peak current density, relative to the size of the stimulation source, was largest for EBS. Conclusion: In order to maximize therapeutic efficiency, neurostimulation trials need to account for the impact of anatomically disrupted neural tissues on the location, orientation, and magnitude of exogenously applied currents. The relative current-neuronal structure should be considered when planning stimulation treatment, especially across techniques (e.g., using TMS to predict EBS response). We postulate that the effects of altered tissue properties in stroke regions may impact stimulation induced analgesic effects and/or lead to highly variable outcomes during brain stimulation treatments in CPSP.

The composition of the inner nuclear layer of the cat retina.

The cellular composition of the inner nuclear layer (INL) is largely conserved among mammals. Studies of rabbit, monkey, and mouse retinas have shown that bipolar, amacrine, Müller, and horizontal cells make up constant fractions of the INL (42, 35, 20, and 3%, respectively); these proportions remain relatively constant at all retinal eccentricities. The purpose of our study was to test whether the organization of cat retina is similar to that of other mammalian retinas. Fixed retinas were embedded in plastic, serially sectioned at a thickness of 1 microm, stained, and imaged at high power in the light microscope. Bipolar, amacrine, Müller, and horizontal cells were classified and counted according to established morphological criteria. Additional sets of sections were processed for protein kinase C and calretinin immunoreactivity to determine the relative fraction of rod bipolar and AII amacrine cells. Our results show that the organization of INL in the cat retina contains species-specific alterations in the composition of the INL tied to the large fraction of rod photoreceptors. Compared with other mammalian retinas, cat retinas show an expansion of the rod pathway with rod bipolar cells accounting for about 70% of all bipolar cells and AII cells accounting for nearly a quarter of all amacrine cells. Our results suggest that evolutionary pressures in cats over time have refined their retinal organization to suit its ecological niche.

Benefit of multiple sessions of perilesional repetitive transcranial magnetic stimulation for an effective rehabilitation of visuospatial function

Noninvasive neurostimulation techniques have been used alone or in conjunction with rehabilitation therapy to treat the neurological sequelae of brain damage with rather variable therapeutic outcomes. One potential factor limiting a consistent success for such techniques may be the limited number of sessions carried out in patients, despite reports that their accrual may play a key role in alleviating neurological deficits long‐term. In this study, we tested the effects of seventy consecutive sessions of perilesional high‐frequency (10 Hz) repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic neglect deficits in a well‐established feline model of visuospatial neglect. Under identical rTMS parameters and visuospatial testing regimes, half of the subjects improved in visuospatial orienting performance. The other half experienced either none or extremely moderate ameliorations in the neglected hemispace and displayed transient patterns of maladaptive visuospatial behavior. Detailed analyses suggest that lesion location and extent did not account for the behavioral differences observed between these two groups of animals. We conclude that multi‐session perilesional rTMS regimes have the potential to induce functional ameliorations following focal chronic brain injury, and that behavioral performance prior to the onset of the rTMS treatment is the factor that best predicts positive outcomes for noninvasive neurostimulation treatments in visuospatial neglect.

Age-Dependent Sparing of Visual Function After Bilateral Lesions of Primary Visual Cortex

Bilateral lesions of primary visual cortex (PVC) sustained early in life induce the visual system to undergo structural and functional reorganization and produce modified neuronal networks capable of mediating visual abilities that would be impaired if the lesions occurred in adulthood. Reorganization after early lesion is also accompanied by degeneration of the lateral geniculate nucleus of the thalamus, and 90% of beta retinal ganglion cells die via retrograde degeneration. It is unclear whether the high potential of the system to reorganize after early lesion could overcome the effects of beta retinal ganglion cell death. Visual acuity, which depends on an intact beta-cell array, was impaired in cats that underwent PVC lesions on postnatal day 1 and indicated that neuroplastic potential was insufficient to overcome early lesion-induced maladaptive plasticity. Animals with lesions made at 1 month of age, a stage accompanied by high levels of neuroplastic potential but no death of beta cells, achieved acuity measures equivalent to intact animals. The authors conclude that visual signals are rerouted to subserve functionality when the lesion is made at 1 month of age, but not at 1 day of age.

The Special Relationship between β Retinal Ganglion Cells and Cat Primary Visual Cortex

Publisher Summary This chapter summarizes the characteristics of cat ganglion cells that are vulnerable and those that appear to be largely insensitive to the cortical lesion. It reviews the relevant features of retinal ganglion structure, function, contributions to vision, and connectivity and also describes the impact of primary visual cortex lesions on ganglion cells and visually guided behavior. The elimination of β (X) cells has a potentially profound impact on visual processing in addition to the absence of primary visual cortex. The three most significant factors linked to the survival, and death of cat retinal ganglion cells following lesions of primary visual cortex are maturational status, patterns of connectivity, and rate of degeneration of lateral geniculate nucleus (LGN) neurons. β (X)-retinal ganglion cells in the cat and monkey, and by extension humans, have a unique and a signature array of morphological, physiological, and connectional characteristics that set them apart from all other ganglion cell types. They are also extremely fragile and depend for survival on primary visual cortex and its intermediate relay structure, the LGN, both some distance apart.