Stephen G. Lomber

Impact of repetitive transcranial magnetic stimulation of the parietal cortex on metabolic brain activity: a 14C-2DG tracing study in the cat

Transcranial magnetic stimulation (TMS) is increasingly utilized in clinical neurology and neuroscience. However, detailed knowledge of the impact and specificity of the effects of TMS on brain activity remains unresolved. We have used 14C-labeled deoxyglucose (14C-2DG) mapping during repetitive TMS (rTMS) of the posterior and inferior parietal cortex in anesthetized cats to study, with exquisite spatial resolution, the local and distant effects of rTMS on brain activity. High-frequency rTMS decreases metabolic activity at the primary site of stimulation with respect to homologue areas in the unstimulated hemisphere. In addition, rTMS induces specific distant effects on cortical and subcortical regions known to receive substantial efferent projections from the stimulated cortex. The magnitude of this distal impact is correlated with the strength of the anatomical projections. Thus, in the anesthetized animal, the impact of rTMS is upon a distributed network of structures connected to the primary site of application.

Reconstructing functional systems after lesions of cerebral cortex

The young brain is enormously resilient to early injury. This resiliency contrasts with the severe and permanent impairments that frequently accompany equivalent damage to the mature cerebrum. For example, damage to Brocas area renders the patient unable to speak, but equivalent damage early in life does not have such devastating effects. Here we review the history of the study of early lesion-induced plasticity, and delineate the features of the developing brain that permit it to overcome the effects of early cerebral lesions. We also speculate on future avenues of investigation that should help us to comprehend how young brains are naturally rebuilt after early lesions.

Restoration of visual orienting into a cortically blind hemifield by reversible deactivation of posterior parietal cortex or the superior colliculus

Abstract. A contralateral hemineglect of the visual field can be induced by unilateral cooling deactivation of posterior middle suprasylvian (pMS) sulcal cortex of the posterior parietal region, and this neglect can be reversed by additional cooling deactivation of pMS cortex in the opposite hemisphere. The purpose of the present study was to test whether an enduring hemianopia induced by removal of all contiguous visual cortical areas of one hemisphere could be reversed by local cooling of pMS cortex in the opposite hemisphere. Two cats sustained large unilateral ablations of the contiguous visual areas, and cooling loops were placed in the pMS sulcus, and in contact with adjacent areaxa07 or posterior ectosylvian (PE) cortex of the opposite hemisphere. In both instances cooling of pMS cortex, but neither areaxa07 nor PE, restored a virtually normal level of orienting performance to stimuli presented anywhere in the previously hemianopic field. The reversal was highly sensitive to the extent of cooling deactivation. In a third cat, cooling deactivation of the superficial layers of the contralateral superior colliculus also restored orienting performance to a cortical ablation-induced hemianopia. This reversal was graded from center-to-periphery in a temperature-dependent manner. Neither the cortical ablation nor any of the cooling deactivations had any impact on an auditory detection and orienting task. The deactivations were localized and confirmed by reduced uptake of radiolabeled 2-deoxyglucose to be limited to the immediate vicinity of each cooling loop. The results are discussed in terms of excitation and disinhibition of visual circuits.

Cerebral areas mediating visual redirection of gaze: Cooling deactivation of 15 loci in the cat

In humans, damage to posterior parietal or frontal cortices often induces a severe impairment of the ability to redirect gaze to visual targets introduced into the contralateral field. In cats, unilateral deactivation of the posterior middle suprasylvian (pMS) sulcus in the posterior inferior parietal region also results in an equally severe impairment of visually mediated redirection of gaze. In this study we tested the contributions of the pMS cortex and 14 other cortical regions in mediating redirection of gaze to visual targets in 31 adult cats. Unilateral cooling deactivation of three adjacent regions along the posterior bend of the suprasylvian sulcus (posterior middle suprasylvian sulcus, posterior suprasylvian sulcus, and dorsal posterior ectosylvian gyrus at the confluence of the occipital, parietal, and temporal cortices) eliminated visually mediated redirection of gaze towards stimuli introduced into the contralateral hemifield, while the redirection of gaze toward the ipsilateral hemifield remained highly proficient. Additional cortical loci critical for visually mediated redirection of gaze include the anterior suprasylvian gyrus (lateral area 5, anterior inferior parietal cortex) and medial area 6 in the frontal region. Cooling deactivation of: 1) dorsal or 2) ventral posterior suprasylvian gyrus; 3) ventral posterior ectosylvian gyrus, 4) middle ectosylvian gyrus; 5) anterior or 6) posterior middle suprasylvian gyrus (area 7); 7) anterior middle suprasylvian sulcus; 8) medial area 5; 9) the visual portion of the anterior ectosylvian sulcus (AES); 10) or lateral area 6 were all without impact on the ability to redirect gaze. In summary, we identified a prominent field of cortex at the junction of the temporo‐occipito‐parietal cortices (regions pMS, dPE, PS), an anterior inferior parietal field (region 5L), and a frontal field (region 6M) that all contribute critically to the ability to redirect gaze to novel stimuli introduced into the visual field during fixation. These loci have several features in common with cortical fields in monkey and human brains that contribute to the visually guided redirection of the head and eyes. J. Comp. Neurol. 474:190–208, 2004.

Cancellation of visuoparietal lesion-induced spatial neglect

In humans lesions of right visuoparietal cortex induce a neglect of the contralesional visual field that is characterized in its mild form by inattentiveness to objects and events and, in its more severe form, by a condition that has many features that are indistinguishable from blindness. Here we show that spatial neglect can be induced in cats by lesions of posterior and inferior visuoparietal cortex, and that the lesion-induced neglect can be cancelled by cooling deactivation of the same region in the opposite hemisphere.

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.

Quantitative analyses of principal and secondary compound parieto-occipital feedback pathways in cat

The purpose of our study was to quantify the magnitude of principal and secondary pathways emanating from the middle suprasylvian (MS) region of visuoparietal cortex and terminating in area 18 of primary visual cortex. These pathways transmit feedback signals from visuoparietal cortex to primary visual cortex. (1) WGA-HRP was injected into area 18 to identify inputs from visual structures. In terms of numbers of neurons, feedback projections to area 18 from MS sulcal cortex (areas PMLS, AMLS and PLLS) comprise 26% of inputs from all visual structures. Of these neurons, between 21% and 34.9% are located in upper layers 2–4 and the dominant numbers are located in deep layers 5 and 6. Areas 17 (11.8%) and 19 (11.2%) provide more modest cortical inputs, and another eight areas provide a combined total of 4.3% of inputs. The sum of neurons in all subcompartments of the lateral geniculate nucleus (LGN) accounts for another 34.8% of the input to area 18, whereas inputs from the lateral division of the lateral-posterior nucleus (LPl) account for the final 11.9%. (2) Injection of tritiated-(3H)-amino acids into MS sulcal cortex revealed substantial direct projections from MS cortex that terminated in all layers of area 18, but with a markedly lower density in layer 4. Projections from MS cortex to both areas 17 and 19 are of similar density and characteristics, whereas those to other cortical targets have very low densities. Quantification also revealed minor-to-modest axon projections to all components of LGN and a massive projection throughout the LP-Pul complex. (3) Superposition of the labeled terminal and cell fields identified secondary, compound feedback pathways from MS cortex to area 18. The largest secondary pathway is massive and it includes the LPl nucleus. Much more modest secondary pathways include areas 17 and 19, and LGN. The relative magnitudes of the secondary pathways suggest that the one through LPl exerts a major influence on area 18, whereas the others exert more modest or minor influences. MS cortex in the contralateral hemisphere also innervates area 18 directly. These data are important for interpreting the impact of deactivating feedback projections from visuoparietal cortex on occipital cortex.

Relocation of specific visual functions following damage of mature posterior parietal cortex.

Many visual deficits have been reported following damage to specific cerebral sites within posterior parietal cortex. These deficits generally involve aspects of vision including spatial or motion perception and visuomotor control. One characteristic of many of these deficits is that they tend to attenuate over time. Presumably, other cortical regions possess adaptive neuroplastic mechanisms that allow them to accommodate functions that were previously dominated by the damaged region. This report summarizes a series of experiments that examined adaptive cortical plasticity following cerebral cortex damage sustained in maturity. Following bilateral lesions of posterior middle suprasylvian sulcal (pMSs) cortex in the cat, deficits were identified in both visual orienting and landmark discrimination tasks. However, the deficits on the visual orienting task were only profound for the first few days following the lesion and orienting abilities returned to normal levels within the first 2 weeks postlesion. In contrast, no such attenuation of the effect of the lesion was evident on the landmark discrimination task. Following recovery of function on the visual orienting task, individual cortical areas flanking the lesion were bilaterally deactivated with cooling. Reversible deactivation of anterior middle suprasylvian sulcal (aMSs) cortex, but none of the other adjacent cortices, yielded visual orienting deficits that are not found in intact animals during deactivation of aMSs cortex. Therefore, we concluded that the visual orienting functions normally mediated by pMSs cortex were able to relocate to aMSs cortex following lesion of pMSs cortex. Finally, bilateral lesion of both pMSs and aMSs cortices yielded visual orienting deficits that did not attenuate. Overall, this series of experiments demonstrates that certain visual functions may relocate to specific cortical loci following damage to discrete areas within posterior parietal cortex.