Multiple sessions of transcranial direct current stimulation to the intact hemisphere improves visual function after unilateral ablation of visual cortex

Damage to cerebral systems is frequently followed by the emergence of compensatory mechanisms, which serve to reduce the effects of brain damage and allow recovery of function. Intrinsic recovery, however, is rarely complete. Non-invasive brain stimulation technologies have the potential to actively shape neural circuits and enhance recovery from brain damage. In this study, a stable deficit for detecting and orienting to visual stimuli presented in the contralesional visual hemifield was generated by producing unilateral brain damage of the right posterior parietal and contiguous visual cortical areas. A long regimen of inhibitory non-invasive transcranial directcurrent stimulation (cathodal 2mA, 20 min) was applied to the contralateral (intact) posterior parietal cortex over 14 weeks (total of 70 sessions, one per day, five days per week) and behavioral outcomes were periodically assessed. In three out of four stimulated cats, lasting recovery of visuospatial function was observed. Recovery started after 2-3 weeks of stimulation, and recovered targets were located first in the periphery, and moved to more central visual field locations with the accrual of stimulation sessions. Recovery for moving tasks followed a biphasic pattern before reaching plateau levels. Recovery did not occur for more difficult visual tasks. These findings highlight the ability of multiple sessions of transcranial direct-current stimulation to produce recovery of visuospatial function after unilateral brain damage

GradICON\texttt{GradICON}: Approximate Diffeomorphisms via Gradient Inverse Consistency

We present an approach to learning regular spatial transformations between image pairs in the context of medical image registration. Contrary to optimization-based registration techniques and many modern learning-based methods, we do not directly penalize transformation irregularities but instead promote transformation regularity via an inverse consistency penalty. We use a neural network to predict a map between a source and a target image as well as the map when swapping the source and target images. Different from existing approaches, we compose these two resulting maps and regularize deviations of the $\bf{Jacobian}$ of this composition from the identity matrix. This regularizer -- $\texttt{GradICON}$ -- results in much better convergence when training registration models compared to promoting inverse consistency of the composition of maps directly while retaining the desirable implicit regularization effects of the latter. We achieve state-of-the-art registration performance on a variety of real-world medical image datasets using a single set of hyperparameters and a single non-dataset-specific training protocol.Comment: 29 pages, 16 figures, CVPR 202

Reconstructing the somatotopic organization of the corticospinal tract remains a challenge for modern tractography methods

The corticospinal tract (CST) is a critically important white matter fiber tract in the human brain that enables control of voluntary movements of the body. Diffusion MRI tractography is the only method that enables the study of the anatomy and variability of the CST pathway in human health. In this work, we explored the performance of six widely used tractography methods for reconstructing the CST and its somatotopic organization. We perform experiments using diffusion MRI data from the Human Connectome Project. Four quantitative measurements including reconstruction rate, the WM-GM interface coverage, anatomical distribution of streamlines, and correlation with cortical volumes to assess the advantages and limitations of each method. Overall, we conclude that while current tractography methods have made progress toward the well-known challenge of improving the reconstruction of the lateral projections of the CST, the overall problem of performing a comprehensive CST reconstruction, including clinically important projections in the lateral (hand and face area) and medial portions (leg area), remains an important challenge for diffusion MRI tractography.Comment: 41 pages, 19 figure

A Novel Deep Clustering Framework for Fine-Scale Parcellation of Amygdala Using dMRI Tractography

The amygdala plays a vital role in emotional processing and exhibits structural diversity that necessitates fine-scale parcellation for a comprehensive understanding of its anatomico-functional correlations. Diffusion MRI tractography is an advanced imaging technique that can estimate the brain's white matter structural connectivity to potentially reveal the topography of the amygdala for studying its subdivisions. In this work, we present a deep clustering pipeline to perform automated, fine-scale parcellation of the amygdala using diffusion MRI tractography. First, we incorporate a newly proposed deep learning approach to enable accurate segmentation of the amygdala directly on the dMRI data. Next, we design a novel streamline clustering-based structural connectivity feature for a robust representation of voxels within the amygdala. Finally, we improve the popular joint dimensionality reduction and k-means clustering approach to enable amygdala parcellation at a finer scale. With the proposed method, we obtain nine unique amygdala parcels. Experiments show that these parcels can be consistently identified across subjects and have good correspondence to the widely used coarse-scale amygdala parcellation

Impact of brain tissue filtering on neurostimulation fields: A modeling study

Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson's disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods.United States. Defense Advanced Research Projects Agency (Contract W31P4Q-09-C-0117)National Institute of Neurological Disorders and Stroke (U.S.) (Award R43NS062530)National Institute of Neurological Disorders and Stroke (U.S.) (Award 1R44NS080632

Prenatal Protein Malnutrition Leads to Hemispheric Differences in the Extracellular Concentrations of Norepinephrine, Dopamine and Serotonin in the Medial Prefrontal Cortex of Adult Rats

Exposure to prenatal protein malnutrition (PPM) leads to a reprogramming of the brain, altering executive functions involving the prefrontal cortex (PFC). In this study we used in vivo microdialysis to assess the effects of PPM on extracellular concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) bilaterally in the ventral portion of the medial prefrontal cortex (vmPFC; ventral prelimbic and infralimbic cortices) of adult Long-Evans rats. Female Long-Evans rats were fed either a low protein (6%) or adequate protein diet (25%) prior to mating and throughout pregnancy. At birth, all litters were culled and fostered to dams fed a 25% (adequate) protein diet. At 120 days of age, 2 mm microdialysis probes were placed into left and right vmPFC. Basal extracellular concentrations of NE, DA, and 5-HT were determined over a 1-h period using HPLC. In rats exposed to PPM there was a decrease in extracellular concentrations of NE and DA in the right vmPFC and an increase in the extracellular concentration of 5-HT in the left vmPFC compared to controls (prenatally malnourished: N = 10, well-nourished: N = 20). Assessment of the cerebral laterality of extracellular neurotransmitters in the vmPFC showed that prenatally malnourished animals had a significant shift in laterality from the right to the left hemisphere for NE and DA but not for serotonin. In a related study, these animals showed cognitive inflexibility in an attentional task. In animals in the current study, NE levels in the right vmPFC of well-nourished animals correlated positively with performance in an attention task, while 5-HT in the left vmPFC of well-nourished rats correlated negatively with performance. These data, in addition to previously published studies, suggest a long-term reprogramming of the vmPFC in rats exposed to PPM which may contribute to attention deficits observed in adult animals exposed to PPM

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. Non-invasive 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 few sessions carried out in patients, despite reports that their accrual may play a key role in alleviating neurological deficits long-term

Facilitation paradoxale induite par la perturbation de la fonction visuo-spatiale: revisiter «l’effet Sprague»

International audienceThe ‘Sprague Effect’ described in the seminal paper of James Sprague (Science 153:1544 e1547, 1966a) is an unexpected paradoxical effect in which a second brain lesion reversed functional deficits induced by an earlier lesion. It was observed initially in the cat where severe and permanent contralateral visually guided attentional deficits generated by the ablation of large areas of the visual cortex were reversed by the subsequent removal of the superior colliculus (SC) opposite to the cortical lesion or by the splitting of the collicular commissure. Physiologically, this effect has been explained in several ways-most notably by the reduction of the functional inhibition of the ipsilateral SC by the contralateral SC, and the restoration of normal interactions between cortical and midbrain structures after ablation. In the present review, we aim at reappraising the ‘Sprague Effect’ by critically analyzing studies that have been conducted in the feline and human brain. Moreover, we assess applications of the ‘Sprague Effect’ in the rehabilitation of visually guided atten- tional impairments by using non-invasive therapeutic approaches such as transcranial magnetic stimulation (TMS) and transcranial direct-current stimulation (tDCS). We also review theoretical models of the effect that emphasize the inhibition and balancing be- tween the two hemispheres and show implications for lesion inference approaches. Last, we critically review whether the resulting inter-hemispheric rivalry theories lead toward an efficient rehabilitation of stroke in humans. We conclude by emphasizing key challenges in the field of ‘Sprague Effect’ applications in order to design better therapies for brain-damaged patients.L’effet Sprague décrit dans le document fondateur de James Sprague (Science 153: 1544 e1547, 1966a) est un effet paradoxal inattendu dans lequel une deuxième lésion cérébrale inversait les déficits fonctionnels induits par une lésion antérieure. Il a été observé initialement chez le chat où les déficits attentionnels controlatéraux sévères et permanents générés par l'ablation de grandes zones du cortex visuel ont été inversés par l'ablation ultérieure du colliculus supérieur (SC) opposé à la lésion corticale ou par la division de la commissure colliculaire. Physiologiquement, cet effet a été expliqué de plusieurs façons, notamment par la réduction de l'inhibition fonctionnelle de la SC ipsilatérale par la SC controlatérale et la restauration des interactions normales entre les structures corticales et du mésencéphale après l'ablation. Dans la présente revue, nous visons à réévaluer «l’effet Sprague» en analysant de manière critique les études qui ont été menées sur le cerveau félin et humain. De plus, nous évaluons les applications de «l’effet Sprague» dans la réadaptation des troubles de l’attention guidés visuellement en utilisant des approches thérapeutiques non invasives telles que la stimulation magnétique transcrânienne (TMS) et la stimulation transcrânienne à courant continu (tDCS). Nous passons également en revue les modèles théoriques de l'effet qui mettent l'accent sur l'inhibition et l'équilibre entre les deux hémisphères et montrent les implications pour les approches d'inférence des lésions. Enfin, nous examinons de manière critique si les théories de rivalité interhémisphérique qui en résultent conduisent à une réhabilitation efficace de l'AVC chez l'homme. Nous concluons en mettant l’accent sur les principaux défis dans le domaine des applications de «l’effet Sprague» afin de concevoir de meilleures thérapies pour les patients atteints de lésions cérébrales

Characterization of Visual Percepts Evoked by Noninvasive Stimulation of the Human Posterior Parietal Cortex

Phosphenes are commonly evoked by transcranial magnetic stimulation (TMS) to study the functional organization, connectivity, and excitability of the human visual brain. For years, phosphenes have been documented only from stimulating early visual areas (V1–V3) and a handful of specialized visual regions (V4, V5/MT+) in occipital cortex. Recently, phosphenes were reported after applying TMS to a region of posterior parietal cortex involved in the top-down modulation of visuo-spatial processing. In the present study, we systematically characterized parietal phosphenes to determine if they are generated directly by local mechanisms or emerge through indirect activation of other visual areas. Using technology developed in-house to record the subjective features of phosphenes, we found no systematic differences in the size, shape, location, or frame-of-reference of parietal phosphenes when compared to their occipital counterparts. In a second experiment, discrete deactivation by 1 Hz repetitive TMS yielded a double dissociation: phosphene thresholds increased at the deactivated site without producing a corresponding change at the non-deactivated location. Overall, the commonalities of parietal and occipital phosphenes, and our ability to independently modulate their excitability thresholds, lead us t