Mark A. Halko

Visual Topography of Human Intraparietal Sulcus

Human parietal cortex is implicated in a wide variety of sensory and cognitive functions, yet its precise organization remains unclear. Visual field maps provide a potential structural basis for descriptions of functional organization. Here, we detail the topography of a series of five maps of the contralateral visual hemifield within human posterior parietal cortex. These maps are located along the medial bank of the intraparietal sulcus (IPS) and are revealed by direct visual stimulation during functional magnetic resonance imaging, allowing these parietal regions to be routinely and reliably identified simultaneously with occipital visual areas. Two of these maps (IPS3 and IPS4) are novel, whereas two others (IPS1 and IPS2) have previously been revealed only by higher-order cognitive tasks. Area V7, a previously identified visual map, is observed to lie within posterior IPS and to share a foveal representation with IPS1. These parietal maps are reliably observed across scan sessions; however, their precise topography varies between individuals. The multimodal organization of posterior IPS mirrors this variability in visual topography, with complementary tactile activations found immediately adjacent to the visual maps both medially and laterally. These visual maps may provide a practical framework in which to characterize the functional organization of human IPS.

Characterizing Brain Cortical Plasticity and Network Dynamics Across the Age-Span in Health and Disease with TMS-EEG and TMS-fMRI

Brain plasticity can be conceptualized as nature’s invention to overcome limitations of the genome and adapt to a rapidly changing environment. As such, plasticity is an intrinsic property of the brain across the lifespan. However, mechanisms of plasticity may vary with age. The combination of transcranial magnetic stimulation (TMS) with electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) enables clinicians and researchers to directly study local and network cortical plasticity, in humans in vivo, and characterize their changes across the age-span. Parallel, translational studies in animals can provide mechanistic insights. Here, we argue that, for each individual, the efficiency of neuronal plasticity declines throughout the age-span and may do so more or less prominently depending on variable ‘starting-points’ and different ‘slopes of change’ defined by genetic, biological, and environmental factors. Furthermore, aberrant, excessive, insufficient, or mistimed plasticity may represent the proximal pathogenic cause of neurodevelopmental and neurodegenerative disorders such as autism spectrum disorders or Alzheimer’s disease.

Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS)

Both resting state functional magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS) are increasingly popular techniques that can be used to non-invasively measure brain connectivity in human subjects. TMS shows additional promise as a method to manipulate brain connectivity. In this review we discuss how these two complimentary tools can be combined to optimally study brain connectivity and manipulate distributed brain networks. Important clinical applications include using resting state fcMRI to guide target selection for TMS and using TMS to modulate pathological network interactions identified with resting state fcMRI. The combination of TMS and resting state fcMRI has the potential to accelerate the translation of both techniques into the clinical realm and promises a new approach to the diagnosis and treatment of neurological and psychiatric diseases that demonstrate network pathology.

Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner

Intrinsic activity in the brain is organized into networks. Although constrained by their anatomical connections, functional correlations between nodes of these networks reorganize dynamically. Dynamic organization implies that couplings between network nodes can be reconfigured to support processing demands. To explore such reconfigurations, we combined repetitive transcranial magnetic stimulation (rTMS) and functional connectivity MRI (fcMRI) to modulate cortical activity in one node of the default network, and assessed the effect of this upon functional correlations throughout the network. Two different frequencies of rTMS to the same default network node (the left posterior inferior parietal lobule, lpIPL) induced two topographically distinct changes in functional connectivity. High-frequency rTMS to lpIPL decreased functional correlations between cortical default network nodes, but not between these nodes and the hippocampal formation. In contrast, low frequency rTMS to lpIPL did not alter connectivity between cortical default network nodes, but increased functional correlations between lpIPL and the hippocampal formation. These results suggest that the default network is composed of (at least) two subsystems. More broadly, the finding that two rTMS stimulation regimens to the same default network node have distinct effects reveals that this node is embedded within a network that possesses multiple, functionally distinct relationships among its distributed partners.

Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS

Transcranial direct current stimulation (tDCS) has recently emerged as a promising approach to enhance neurorehabilitative outcomes. However, little is known about how the local electrical field generated by tDCS relates to underlying neuroplastic changes and behavior. To address this question, we present a case study analysis of an individual with hemianopia due to stroke and who benefited from a combined visual rehabilitation training and tDCS treatment program. Activation associated with a visual motion perception task (obtained by functional magnetic resonance imaging; fMRI) was used to characterize local changes in brain activity at baseline and after training. Individualized, high-resolution electrical field modeling reproducing precise cerebral and lesioned tissue geometry, predicted distortions of current flow in peri-lesional areas and diffuse clusters of peak electric fields. Using changes in fMRI signal as an index of cortical recovery, correlations to the electrical field map were determined. Significant correlations between the electrical field and change in fMRI signal were region specific including cortical areas under the anode electrode and peri-lesional visual areas. These patterns were consistent with effective tDCS facilitated rehabilitation. We describe the methodology used to analyze tDCS mechanisms through combined fMRI and computational modeling with the ultimate goal of developing a rationale for individualized therapy.

Intermittent theta-burst stimulation of the lateral cerebellum increases functional connectivity of the default network.

Cerebral cortical intrinsic connectivity networks share topographically arranged functional connectivity with the cerebellum. However, the contribution of cerebellar nodes to distributed network organization and function remains poorly understood. In humans, we applied theta-burst transcranial magnetic stimulation, guided by subject-specific connectivity, to regions of the cerebellum to evaluate the functional relevance of connections between cerebellar and cerebral cortical nodes in different networks. We demonstrate that changing activity in the human lateral cerebellar Crus I/II modulates the cerebral default mode network, whereas vermal lobule VII stimulation influences the cerebral dorsal attention system. These results provide novel insights into the distributed, but anatomically specific, modulatory impact of cerebellar effects on large-scale neural network function.

Combining Visual Rehabilitative Training and Noninvasive Brain Stimulation to Enhance Visual Function in Patients With Hemianopia: A Comparative Case Study

To standardize a protocol for promoting visual rehabilitative outcomes in post‐stroke hemianopia by combining occipital cortical transcranial direct current stimulation (tDCS) with Vision Restoration Therapy (VRT).

Teaching the Blind to Find Their Way by Playing Video Games

Computer based video games are receiving great interest as a means to learn and acquire new skills. As a novel approach to teaching navigation skills in the blind, we have developed Audio-based Environment Simulator (AbES); a virtual reality environment set within the context of a video game metaphor. Despite the fact that participants were naïve to the overall purpose of the software, we found that early blind users were able to acquire relevant information regarding the spatial layout of a previously unfamiliar building using audio based cues alone. This was confirmed by a series of behavioral performance tests designed to assess the transfer of acquired spatial information to a large-scale, real-world indoor navigation task. Furthermore, learning the spatial layout through a goal directed gaming strategy allowed for the mental manipulation of spatial information as evidenced by enhanced navigation performance when compared to an explicit route learning strategy. We conclude that the immersive and highly interactive nature of the software greatly engages the blind user to actively explore the virtual environment. This in turn generates an accurate sense of a large-scale three-dimensional space and facilitates the learning and transfer of navigation skills to the physical world.

Changes in white matter microstructure in patients with TLE and hippocampal sclerosis

OBJECTIVE Patients with mesial temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS) often show ictal and interictal propagation of epileptiform EEG activity to the ipsilateral temporal neocortex, the ipsilateral frontal lobe or the contralateral hippocampus, although structural MRI only shows unilateral involvement of the hippocampal formation. We used whole-head diffusion Tensor Imaging (DTI) to delineate a network that facilitates propagation of interictal epileptiform and seizure activity in this patient group. METHODS Isotropic 2 mm DTI was performed at 3 Tesla in 12 patients with medically intractable left TLE due to HS and compared to 12 controls. Whole-brain maps of fractional anisotropy (FA) were compared using a voxel based t-test to search for regions affected in patients with HS. This preliminary analysis was complementary to a set of anatomically guided region of interest (ROI) analyses that were manually defined on each individuals FA map. RESULTS Left HS patients showed FA decreases in the temporal lobe white matter bilaterally, the ipsilateral frontal lobe white matter (WM) and in the genu and trunk of the corpus callosum. ROI analysis identified a significant FA decrease in left HS subjects in the affected hippocampus, WM of the ipsilateral parahippocampal gyrus and the genu and trunk of the corpus callosum. CONCLUSION WM alterations occur bilaterally in the temporal lobe and in the ipsilateral superior frontal gyrus in left HS. The etiology and significance of these changes are unclear but the role of these regions in epileptogenesis and for pathways of epileptic spread should be further investigated.

Multiple mechanisms of illusory contour perception

A variety of mechanisms have been proposed to explain illusory contour formation. However, since prior studies have focused on a single mechanism, there is no clear consensus regarding contour formation mechanisms. Here we developed a novel vivid dynamic display we call the chomping pacman that allows measurement of minute differences in contour clarity. This illusion is shown to be more vivid than traditional static displays. Using the method of adjustment, we are able to identify three mechanisms of contour formation: extrapolation, interpolation, and figural. We posit that these three mechanisms combine to form the general illusory contour percept in traditional static Kanizsa displays and likely contribute to real-world contour perception.