Jitendra Sharma

Adaptation-induced plasticity of orientation tuning in adult visual cortex.

A key emergent property of the primary visual cortex (V1) is the orientation selectivity of its neurons. The extent to which adult visual cortical neurons can exhibit changes in orientation selectivity is unknown. Here we use single-unit recording and intrinsic signal imaging in V1 of adult cats to demonstrate systematic repulsive shifts in orientation preference following short-term exposure (adaptation) to one stimulus orientation. In contrast to the common view of adaptation as a passive process by which responses around the adapting orientation are reduced, we show that changes in orientation tuning also occur due to response increases at orientations away from the adapting stimulus. Adaptation-induced orientation plasticity is thus an active time-dependent process that involves network interactions and includes both response depression and enhancement.

Induction of visual orientation modules in auditory cortex.

Modules of neurons sharing a common property are a basic organizational feature of mammalian sensory cortex. Primary visual cortex (V1) is characterized by orientation modules—groups of cells that share a preferred stimulus orientation—which are organized into a highly ordered orientation map. Here we show that in ferrets in which retinal projections are routed into the auditory pathway, visually responsive neurons in ‘rewired’ primary auditory cortex are also organized into orientation modules. The orientation tuning of neurons within these modules is comparable to the tuning of cells in V1 but the orientation map is less orderly. Horizontal connections in rewired cortex are more patchy and periodic than connections in normal auditory cortex, but less so than connections in V1. These data show that afferent activity has a profound influence on diverse components of cortical circuitry, including thalamocortical and local intracortical connections, which are involved in the generation of orientation tuning, and long-range horizontal connections, which are important in creating an orientation map.

Thalamic atrophy and cognition in multiple sclerosis

Objectives: Recent studies have indicated that brain atrophy is more closely associated with cognitive impairment in multiple sclerosis (MS) than are conventional MRI lesion measures. Enlargement of the third ventricle shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus. Previous imaging and pathology studies have demonstrated thalamic involvement in MS. In this study, we tested the hypothesis that thalamic volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function. Methods: We studied 79 patients with MS and 16 normal subjects. A subgroup of 31 MS subjects underwent cognitive testing. The thalamus was segmented in whole from three-dimensional MRI scans. We also determined whole brain atrophy (brain parenchymal fraction), third ventricular width, and whole brain T2-weighted (fluid-attenuated inversion recovery) hyperintense, T1 hypointense, and gadolinium-enhanced lesion volumes. Results: Normalized thalamic volume was 16.8% lower in the MS group (p < 0.0001) vs controls. Cognitive performance in all domains was moderately to strongly related to thalamic volume in the MS group (r = 0.506 to 0.724, p < 0.005), and thalamic volume entered and remained in all regression models predicting cognitive performance. Thalamic volume showed a weak relationship to physical disability score (r = −0.316, p = 0.005). Conclusion: These findings suggest that thalamic atrophy is a clinically relevant biomarker of the neurodegenerative disease process in multiple sclerosis.

Orientation Maps of Subjective Contours in Visual Cortex

Responses to subjective contours in visual cortical areas V1 and V2 in adult cats were investigated by optical imaging of intrinsic signals and single-unit recording. Both V1 and V2 contain maps of the orientation of subjective gratings that have their basis in specific kinds of neuronal responses to subjective orientations. A greater proportion of neurons in V2 than in V1 show a robust response to subjective edges. Through the use of subjective stimuli in which the orientation of the luminance component is invariant, an unmasked V1 response to subjective edges alone can be demonstrated. The data indicate that the processing of subjective contours begins as early as V1 and continues progressively in higher cortical areas.

Dynamics of neuronal sensitivity in visual cortex and local feature discrimination

A striking aspect of natural scenes is that image features such as line orientation are strongly correlated at neighboring spatial locations but not at distant locations. Thus, during the viewing of a scene, eye movements are often accompanied by a change in the orientation structure of the image. How does this behavior influence the discrimination of local features and their encoding by visual cortical neurons? Here we examined the perceived changes in orientation induced by brief exposure to oriented image patterns in monkeys and humans, and then used reverse correlation to investigate dynamic changes in neuronal sensitivity in the primary visual cortex (V1) of behaving monkeys. Whereas brief adaptation to an oriented grating impaired identification of nearby orientations by broadening orientation selectivity and changing the preferred orientation of individual V1 neurons, it actually enhanced the identification of orthogonal orientations by sharpening neuronal selectivity. Hence, successive exposure to image patches of dissimilar spatial structure enhances both the ability to discriminate local features and the encoding of these features by V1 neurons.

The relationship between whole brain volume and disability in multiple sclerosis: A comparison of normalized gray vs. white matter with misclassification correction

We used SPM99 to obtain normalized whole brain volumes of gray matter, white matter, and total parenchyma in patients with multiple sclerosis (MS) (n = 41) and age-/sex-matched normal controls (n = 18). As SPM99s automated gray/white matter volumes were significantly influenced by tissue compartment misclassification due to the effect of MS-related brain lesions, we corrected these automated volumes for misclassification before performing our primary analyses. For MS patients (disease duration = 9.5 +/- 6.3 years; EDSS score = 3.2 +/- 1.8; 25FTW = 6.6 +/- 3.1 s), we also measured lesion load (total T1 hypointense [T1LV] and FLAIR hyperintense lesion volume [FLLV]), central brain atrophy (third ventricular width [TVW] and bicaudate ratio [BCR]), and clinical status (Expanded Disability Status Scale [EDSS] and 25-ft timed walk [25FTW]). Patients with MS had lower gray matter (707 +/- 33 cm(3) [-3.9%], P = 0.003) and total parenchymal volume (1088 +/- 48 cm(3) [-3.8%], P = 0.003), but only a trend for lower white matter volume (381 +/- 25 cm(3) [-3.7%], P = 0.052) relative to normal controls (gray matter: 736 +/- 33 cm(3); total parenchyma: 1132 +/- 49 cm(3); white matter: 396 +/- 26 cm(3)). Gray matter atrophy was related to clinical status (EDSS, 25FTW, and disease duration), lesion load (T1LV and FLLV), and central brain atrophy (TVW and BCR), whereas white matter atrophy was related to only central brain atrophy. These findings suggest that gray matter loss is related to other aspects of brain pathology and has more clinical relevance than white matter atrophy in MS.

A semiautomated measure of whole-brain atrophy in multiple sclerosis

Brain atrophy is a proposed MRI marker of irreversible pathologic damage in multiple sclerosis (MS). The brain parenchymal fraction (BPF) is the ratio of brain parenchymal volume to the total volume within the surface contour. We developed a semiautomated measure of BPF using commercially available edge-finding and thresholding software (30-min analysis time per patient). We measured BPF in 78 patients with MS and 17 healthy controls. BPF was lower in a cohort of patients with MS (n=50) (0.843+/-0.042, range 0.743-0.906) age-matched to controls (0.877+/-0.020, range 0.835-0.901) (p<0.001). BPF correlated inversely with third ventricular width (r=-0.785, p<0.001), and total T1 hypointense lesion volume (r=-0.347, p=0.011), but not with total T2 hyperintense lesion volume (r=-0.213, p=0.13). BPF correlated negatively with expanded disability status scale (EDSS) score (r=-0.391, p=0.0006) and disease duration (r=-0.281, p=0.01). Stepwise regression compared the relative abilities of MRI variables to predict clinical data. By regression of age, BPF, third ventricular width, T2 lesions, and T1 lesions, BPF was the best predictor of disability score (R(2)=0.204, p<0.001). Third ventricular width was the best predictor of disease duration (R(2)=0.316, p<0.001). None of the MRI variables differed between relapsing-remitting (RR) (n=60) and secondary progressive (SP) (n=18) disease course (p>0.05). The intrarater, interrater, and scan-rescan BPF variability (COV) was 0.31%, 0.34%, and 0.41% and the accuracy against a phantom was 99.1%. We conclude that whole-brain atrophy in MS can be reliably and readily quantified by a semiautomated approach. Longitudinal studies are warranted to determine if this method provides a sensitive biologic marker of the MS disease process.

Nucleus basalis-enabled stimulus-specific plasticity in the visual cortex is mediated by astrocytes

Although cholinergic innervation of the cortex by the nucleus basalis (NB) is known to modulate cortical neuronal responses and instruct cortical plasticity, little is known about the underlying cellular mechanisms. Using cell-attached recordings in vivo, we demonstrate that electrical stimulation of the NB, paired with visual stimulation, can induce significant potentiation of visual responses in excitatory neurons of the primary visual cortex in mice. We further show with in vivo two-photon calcium imaging, ex vivo calcium imaging, and whole-cell recordings that this pairing-induced potentiation is mediated by direct cholinergic activation of primary visual cortex astrocytes via muscarinic AChRs. The potentiation is absent in conditional inositol 1,4,5 trisphosphate receptor type 2 KO mice, which lack astrocyte calcium activation, and is stimulus-specific, because pairing NB stimulation with a specific visual orientation reveals a highly selective potentiation of responses to the paired orientation compared with unpaired orientations. Collectively, these findings reveal a unique and surprising role for astrocytes in NB-induced stimulus-specific plasticity in the cerebral cortex.

Rewiring cortex: The role of patterned activity in development and plasticity of neocortical circuits

Visually driven activity is not required for the establishment of ocular dominance columns, orientation columns, and long-range horizontal connections in visual cortex, although spontaneous activity appears to be necessary. The role of activity may be instructive or simply permissive; evidence for an instructive role requires inquiry into the role of the pattern of activity in shaping cortical circuits. The few experiments that have probed the role of patterned activity include the effects of artificial strabismus, artificial stimulation of the optic nerve, and rewiring visual projections from the retina to the auditory thalamus and cortex. These experiments demonstrate that patterned activity is vital for the maintenance of thalamocortical, local intracortical, and long-range horizontal connections in cortex.

Use of a vascular reconstruction device to salvage acute ischemic occlusions refractory to traditional endovascular recanalization methods.

OBJECT Acute revascularization has been associated with improved stroke outcomes. The Prolyse in Acute Cerebral Thromboembolism (PROACT II) trial achieved recanalization rates of 66%. The Multi Mechanical Embolus Removal in Cerebral Ischemia (Multi MERCI) trial achieved recanalization in 70% of patients. However, these interventional tools are not always successful. The Enterprise vascular reconstruction device was recently introduced for treatment of cerebral aneurysms previously untreatable with endovascular techniques. The authors evaluated a multicenter experience using this stent as a salvage revascularization tool for acute stroke treatment. METHODS Four medical centers participated in a retrospective review of endovascularly treated patients with acute stroke for cases treated with the Enterprise stent after routine interventions had been unsuccessful. Data collected included preprocedure information, intraprocedure findings, and outcomes. RESULTS Twenty patients with acute stroke (mean age 61.6 +/- 22 years) were treated with the Enterprise stent. Ten patients received intravenous recombinant tissue plasminogen activator before catheter intervention, without improvement. Intraarterial interventions attempted unsuccessfully before Enterprise deployment included the Merci retriever (12 patients), angioplasty (7 patients), glycoprotein IIb-IIIa inhibitor administration (12 patients), intraarterial nitroglycerin (1 patient), Wingspan stent deployment (3 patients), and Xpert stent deployment (1 patient). The mean preintervention National Institutes of Health Stroke Scale (NIHSS) score was 17 +/- 6 (median 17). All patients presented with a Thrombolysis in Myocardial Infarction (TIMI) score of 0 or 1. Revascularization was achieved in all patients (75% with a TIMI score of 3, 25% with a TIMI score of 2). Improvement (> or = 4 points on the NIHSS) was documented in 75% of patients. Mean NIHSS improvement from intervention to discharge was 8 +/- 7 points (median 9 points). CONCLUSIONS These preliminary data suggest a potential benefit to the use of the Enterprise stent when routine intervention methods fail.