Search

Functional magnetic resonance imaging (fMRI) of the human brain provides images of changes in local blood flow and oxygenation that are evoked by sensory, motor, or cognitive events. Functional MRI has been used since 1991 [1] to identify areas of the brain that respond to visual stimulation and the performance of vision-related tasks. Increasingly, fMRI is accompanied by diffusion tensor imaging (DTI), which provides images of the speed and direction of diffusion of water molecules in the brain. Fortuitously, this allows remarkable differentiation of cerebral white mater and the delineation of a variety of major white matter tracts including vision-related pathways such as the optic radiations. This chapter focuses primarily on fMRI, but DTI data are also discussed where relevant. Together, the two methods provide a wealth of information about the anatomical and functional status of key components of the visual system in individual patients even in the presence of pathology. For example, an imaging-based map of the visual system can be helpful for planning and guiding surgical resection of tumors impacting critical vision-related brain structures. This is especially true when mass effects or previous surgeries have distorted the normal anatomy making it difficult to know where key structures are located and if they are still functional. In difficult cases, identifying the region of “closest approach” of a planned resection to the cortical representation of central vision or to the optic radiations can help to minimize the risk to eloquent neural tissue and thereby avoid significant treatment-induced vision loss while still permitting maximum therapeutic effect.

Behavioral and personality disorders in temporal lobe epilepsy (TLE) have been a topic of interest and controversy for decades, with less attention paid to alterations in normal personality structure and traits. In this investigation, core personality traits (the Big 5) and their neurobiological correlates in TLE were explored using the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) and structural magnetic resonance imaging (MRI) through the Epilepsy Connectome Project (ECP). NEO-FFI scores from 67 individuals with TLE (34.6 ± 9.5 years; 67% women) were compared to 31 healthy controls (32.8 ± 8.9 years; 41% women) to assess differences in the Big 5 traits (agreeableness, openness, conscientiousness, neuroticism, and extraversion). Individuals with TLE showed significantly higher neuroticism, with no significant differences on the other traits. Neural correlates of neuroticism were then determined in participants with TLE including cortical and subcortical volumes. Distributed reductions in cortical gray matter volumes were associated with increased neuroticism. Subcortically, hippocampal and amygdala volumes were negatively associated with neuroticism. These results offer insight into alterations in the Big 5 personality traits in TLE and their brain-related correlates.

Highlights • TLE patients have older brain ages both functionally and structurally. • Functional brain age is a better predictor of cognitive abilites in TLE patients. • Weaker bilateral frontal/temporal connections affect functional brain aging in TLE. • Functional age mediates some of chronological age-fluid cognition relationships. • Accelerated brain aging in TLE affected by both seizure burden and polytherapy., The association of epilepsy with structural brain changes and cognitive abnormalities in midlife has raised concern regarding the possibility of future accelerated brain and cognitive aging and increased risk of later life neurocognitive disorders. To address this issue we examined age-related processes in both structural and functional neuroimaging among individuals with temporal lobe epilepsy (TLE, N = 104) who were participants in the Epilepsy Connectome Project (ECP). Support vector regression (SVR) models were trained from 151 healthy controls and used to predict TLE patients’ brain ages. It was found that TLE patients on average have both older structural (+6.6 years) and functional (+8.3 years) brain ages compared to healthy controls. Accelerated functional brain age (functional – chronological age) was mildly correlated (corrected P = 0.07) with complex partial seizure frequency and the number of anti-epileptic drug intake. Functional brain age was a significant correlate of declining cognition (fluid abilities) and partially mediated chronological age-fluid cognition relationships. Chronological age was the only positive predictor of crystallized cognition. Accelerated aging is evident not only in the structural brains of patients with TLE, but also in their functional brains. Understanding the causes of accelerated brain aging in TLE will be clinically important in order to potentially prevent or mitigate their cognitive deficits.

The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, foveal acuity is correlated with both a high density of cone photoreceptors at this location and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space—the latter known as the cortical magnification function—steadily decline with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are reduced but appear to be normal in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure cortical magnification in primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied in albinism than previously appreciated, yet cortical magnification outside the fovea is similar to that in controls. Moreover, cortical magnification in albinism and controls exceeds that which might be predicted based on cone density alone, suggesting that reduced foveal cone density in the albinotic retina may be partially counteracted by central connectivity. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in genetic conditions such as albinism.

Retinotopic organization is a fundamental organizational feature of visual cortex thought to play a vital role in encoding spatial location. One important aspect of normal retinotopic organization is the contralateral representation of the right and left hemifields in visual cortex. In human albinism, the temporal retinal afferents decussate pathologically at the optic chiasm resulting in partially superimposed right and left hemifield representations in each hemisphere of visual cortex. Thus, albinism provides a natural model of aberrant retinotopy in which to study the development and function of retinotopic maps. Previous fMRI studies in human albinism suggest that the right and left hemifields are superimposed in a mirror-symmetric manner such that each imaging voxel responds to two regions in visual space mirrored across the vertical meridian. However, to date no group has explicitly attempted to model the receptive field properties of single voxels in albinism. Here we used traditional fMRI retinotopic mapping techniques in conjunction with population receptive field (pRF) modeling in subjects with albinism to fit each voxel’s rotating wedge timecourse in V1-V3 with both single and dual pRF models. We find that most subjects with albinism (but not controls) have sizable clusters of voxels with convincing dual pRFs often corresponding to regions of R-L hemifield overlap. However, not all dual pRFs were mirror symmetrical across the vertical meridian. These asymmetric dual pRFs are not predicted by currently accepted models and suggest that retinocortical miswiring in albinism may be more complicated and heterogenous than previously appreciated. Significance Statement In albinism, the temporal retinal afferents decussate aberrantly at the optic chiasm during development causing partially superimposed right and left hemifield maps in visual cortex. The currently accepted model of retinocortical miswiring in human albinism suggests that these maps are superimposed in a mirror-image fashion such that single locations in visual cortex should respond to two symmetric locations in opposite visual hemifields. To test this, we modeled population receptive fields of individual voxels as single or dual Gaussian sensitivity profiles, fitting the predicted responses to fMRI retinotopic mapping data. For the first time, our results reveal dual pRFs in cortical visual areas V1-V3 in subjects with albinism. However, some subjects had highly asymmetric dual pRFs, indicating that retinocortical miswiring in albinism is more heterogenous and complex than suggested by the “mirror symmetric” model.

Temporal lobe epilepsy (TLE) has been conceptualized as focal disease with a discrete neurobiological focus and can respond well to targeted resection or ablation. In contrast, the neuro-cognitive deficits resulting from TLE can be widespread involving regions beyond the primary epileptic network. We hypothesize that this seemingly paradoxical findings can be explained by differences in connectivity between the primary epileptic region which is hyper-connected and its secondary influence on global connectome organization. This hypothesis is tested using regional and global graph theory metrics where we anticipate that regional mesial-temporal hyperconnectivity will be found and correlate with seizure frequency while global networks will be disorganized and be more closely associated with neuro-cognitive deficits. Resting-state fMRI was used to examine temporal lobe regional connectivity and global functional connectivity from 102 patients with TLE and 55 controls. Connectivity matrices were calculated for subcortical volumes and cortical parcellations. Graph theory metrics (global clustering coefficient (GCC), degree, closeness) were compared between groups and in relation to neuropsychological profiles and disease covariates using permutation testing and causal analysis. In TLE there was a decrease in GCC (p = 0.0345) associated with a worse neuropsychological profile (p = 0.0134). There was increased connectivity in the left hippocampus/amygdala (degree p = 0.0103, closeness p = 0.0104) and a decrease in connectivity in the right lateral temporal lobe (degree p = 0.0186, closeness p = 0.0122). A ratio between the hippocampus/amygdala and lateral temporal lobe—temporal lobe connectivity ratio (TLCR) revealed differences between TLE and controls for closeness (left p = 0.00149, right p = 0.0494) and for degree on left p = 0.00169; with trend on right p = 0.0567. Causal analysis suggested that “Epilepsy Activity” (seizure frequency, anti-seizure medications) was associated with increase in TLCR but not in GCC, while cognitive decline was associated with decreased GCC. These findings support the hypothesis that in TLE there is hyperconnectivity in the hippocampus/amygdala and hypoconnectivity in the lateral temporal lobe associated with “Epilepsy Activity.” While, global connectome disorganization was associated with worse neuropsychological phenotype.

Neuroticism, a core personality trait characterized by a tendency towards experiencing negative affect, has been reported to be higher in people with temporal lobe epilepsy (TLE) compared with healthy individuals. Neuroticism is a known predictor of depression and anxiety, which also occur more frequently in people with TLE. The purpose of this study was to identify abnormalities in whole-brain resting-state functional connectivity in relation to neuroticism in people with TLE and to determine the degree of unique versus shared patterns of abnormal connectivity in relation to elevated symptoms of depression and anxiety. Ninety-three individuals with TLE (55 females) and 40 healthy controls (18 females) from the Epilepsy Connectome Project (ECP) completed measures of neuroticism, depression, and anxiety, which were all significantly higher in people with TLE compared with controls. Resting-state functional connectivity was compared between controls and groups with TLE with high and low neuroticism using analysis of variance (ANOVA) and t-test. In secondary analyses, the same analytics were performed using measures of depression and anxiety and the unique variance in resting-state connectivity associated with neuroticism independent of symptoms of depression and anxiety identified. Increased neuroticism was significantly associated with hyposynchrony between the right hippocampus and Brodmann area (BA) 9 (region of prefrontal cortex (PFC)) (p 0.005), representing a unique relationship independent of symptoms of depression and anxiety. Hyposynchrony of connection between the right hippocampus and BA47 (anterior frontal operculum) was associated with high neuroticism and with higher depression and anxiety scores (p 0.05), making it a shared abnormal connection for the three measures. In conclusion, increased neuroticism exhibits both unique and shared patterns of abnormal functional connectivity with depression and anxiety symptoms between regions of the mesial temporal and frontal lobe.

The human fovea lies at the center of the retina and supports high-acuity vision. In normal visual system development, the highest acuity is correlated with both a high density of cone photoreceptors in the fovea and a magnified retinotopic representation of the fovea in the visual cortex. Both cone density and the cortical area dedicated to each degree of visual space—the latter describing cortical magnification (CM)—steadily decrease with increasing eccentricity from the fovea. In albinism, peak cone density at the fovea and visual acuity are decreased, but seem to be within normal limits in the periphery, thus providing a model to explore the correlation between retinal structure, cortical structure, and behavior. Here, we used adaptive optics scanning light ophthalmoscopy to assess retinal cone density and functional magnetic resonance imaging to measure CM in the primary visual cortex of normal controls and individuals with albinism. We find that retinotopic organization is more varied among individuals with albinism than previously appreciated. Additionally, CM outside the fovea is similar to that in controls, but also more variable. CM in albinism and controls exceeds that which might be predicted based on cone density alone, but is more accurately predicted by retinal ganglion cell density. This finding suggests that decreased foveal cone density in albinism may be partially counteracted by nonuniform connectivity between cones and their downstream signaling partners. Together, these results emphasize that central as well as retinal factors must be included to provide a complete picture of aberrant structure and function in albinism.

Cognitive slowing is a known but comparatively under-investigated neuropsychological complication of the epilepsies in relation to other known cognitive comorbidities such as memory, executive function and language. Here we focus on a novel metric of processing speed, characterize its relative salience compared to other cognitive difficulties in epilepsy, and explore its underlying neurobiological correlates. Research participants included 55 patients with temporal lobe epilepsy (TLE) and 58 healthy controls from the Epilepsy Connectome Project (ECP) who were administered a battery of tests yielding 14 neuropsychological measures, including selected tests from the NIH Toolbox-Cognitive Battery, and underwent 3T MRI and resting state fMRI. TLE patients exhibited a pattern of generalized cognitive impairment with very few lateralized abnormalities. Using the neuropsychological measures, machine learning (Support Vector Machine binary classification model) classified the TLE and control groups with 74% accuracy with processing speed (NIH Toolbox Pattern Comparison Processing Speed Test) the best predictor. In TLE, slower processing speed was associated predominantly with decreased local gyrification in regions including the rostral and caudal middle frontal gyrus, inferior precentral cortex, insula, inferior parietal cortex (angular and supramarginal gyri), lateral occipital cortex, rostral anterior cingulate, and medial orbital frontal regions, as well as three small regions of the temporal lobe. Slower processing speed was also associated with decreased connectivity between the primary visual cortices in both hemispheres and the left supplementary motor area, as well as between the right parieto-occipital sulcus and right middle insular area. Overall, slowed processing speed is an important cognitive comorbidity of TLE associated with altered brain structure and connectivity.

Recent studies have demonstrated significant regional variability in the hemodynamic response function (HRF), highlighting the difficulty of correctly interpreting functional MRI (fMRI) data without proper modeling of the HRF. The focus of this study was to investigate the HRF variability within visual cortex. The HRF was estimated for a number of cortical visual areas by deconvolution of fMRI blood oxygenation level dependent (BOLD) responses to brief, large-field visual stimulation. Significant HRF variation was found across visual areas V1, V2, V3, V4, VO-1,2, V3AB, IPS-0,1,2,3, LO-1,2, and TO-1,2. Additionally, a subpopulation of voxels was identified that exhibited an impulse response waveform that was similar, but not identical, to an inverted version of the commonly described and modeled positive HRF. These voxels were found within the retinotopic confines of the stimulus and were intermixed with those showing positive responses. The spatial distribution and variability of these HRFs suggest a vascular origin for the inverted waveforms. We suggest that the polarity of the HRF is a separate factor that is independent of the suppressive or activating nature of the underlying neuronal activity. Correctly modeling the polarity of the HRF allows one to recover an estimate of the underlying neuronal activity rather than discard the responses from these voxels on the assumption that they are artifactual. We demonstrate this approach on phase-encoded retinotopic mapping data as an example of the benefits of accurately modeling the HRF during the analysis of fMRI data.

fMRI is becoming an important clinical tool for planning and guidance of surgery to treat brain tumors, arteriovenous malformations, and epileptic foci. For visual cortex mapping, the most popular paradigm by far is temporal phase mapping, although random multifocal stimulation paradigms have drawn increased attention due to their ability to identify complex response fields and their random properties. In this study we directly compared temporal phase and multifocal vision mapping paradigms with respect to clinically relevant factors including: time efficiency, mapping completeness, and the effects of noise. Randomized, multifocal mapping accurately decomposed the response of single voxels to multiple stimulus locations and made correct retinotopic assignments as noise levels increased despite decreasing sensitivity. Also, multifocal mapping became less efficient as the number of stimulus segments (locations) increased from 13 to 25 to 49 and when duty cycle was increased from 25% to 50%. Phase mapping, on the other hand, activated more extrastriate visual areas, was more time efficient in achieving statistically significant responses, and had better sensitivity as noise increased, though with an increase in systematic retinotopic mis-assignments. Overall, temporal phase mapping is likely to be a better choice for routine clinical applications though random multifocal mapping may offer some unique advantages for selected applications., Highlights • Phase mapping activates more extrastriate visual areas and is more efficient per run. • Random mapping can decompose the response of single voxels to multiple locations. • Efficiency of random mapping depends on number of stimulus regions and duty cycle. • Noise affects random- and phase-mapping differently.

Functional magnetic resonance imaging studies have significantly expanded the field’s understanding of functional brain activity of healthy and patient populations. Resting state (rs-) fMRI, which does not require subjects to perform a task, eliminating confounds of task difficulty, allows examination of neural activity and offers valuable functional mapping information. The purpose of this work was to develop an automatic resting state network (RNS) labeling method which offers value in clinical workflow during rs-fMRI mapping by organizing and quickly labeling spatial maps into functional networks. Here independent component analysis (ICA) and machine learning were applied to rs-fMRI data with the goal of developing a method for the clinically oriented task of extracting and classifying spatial maps into auditory, visual, default-mode, sensorimotor and executive control resting state networks from 23 epilepsy patients (and for general comparison, separately for 30 healthy subjects). ICA revealed distinct and consistent functional network components across patients and healthy subjects. Network classification was successful, achieving 88% accuracy for epilepsy patients with a naïve Bayes algorithm (and 90% accuracy for healthy subjects with a perceptron). The method’s utility to researchers and clinicians is the provided RSN spatial maps and their functional labeling which offer complementary functional information to clinicians’ expert interpretation.

Previous studies have described the topography of attention-related activation in retinotopic visual cortex for an attended target at one or a few locations within the subject's field of view. However a complete description for all locations in the visual field is lacking. In this human fMRI study, we describe the complete topography of attention-related cortical activation throughout the central 28 degrees of the visual field and compare it with previous models. We cataloged separate fMRI-based maps of attentional topography in medial occipital visual cortex when subjects covertly attended to each target location in an array of three concentric rings of six targets each. We combined the attentional maps for each of the 18 target locations for each subject into a unique composite display to identify common principles of attentional organization for different target locations. Attentional activation was universally highest at the attended target but spread to other segments in a manner depending on eccentricity and/or target size. For targets scaled in size with eccentricity, the attentional effects spread circumferentially as a gradient whose full width at half maximum was consistently 1.5 times the target width at each eccentricity. For targets in the inner (1.8-8.5 degrees) and middle (8.5-15.6 degrees) rings, attention also tended to spread outward, radially to other segments. For targets in the outer ring (15.6-28 degrees), the radial spread of attention was primarily inward to targets of the middle ring. We propose an "attentional landscape" model that is more complex than a "spotlight" or simple "gradient" model but includes aspects of both. Finally, we asked subjects to secretly attend to one of the 18 targets without informing the investigator. We then show that it is possible to determine the target of attentional scrutiny from the pattern of brain activation alone with 100% accuracy. Together, these results provide a comprehensive, quantitative and behaviorally relevant account of the macroscopic cortical topography of visuospatial attention. We also show the pattern of attentional enhancement as it would appear distributed within the observer's field of view thereby permitting direct observation of a neurophysiological correlate of a purely mental phenomenon, the "window of attention".

A perception of coherent motion can be obtained in an otherwise ambiguous or illusory visual display by directing one's attention to a feature and tracking it. We demonstrate an analogous auditory effect in two separate sets of experiments. The temporal dynamics associated with the attention-dependent auditory motion closely matched those previously reported for attention-based visual motion. Since attention-based motion mechanisms appear to exist in both modalities, we also tested for multimodal (audiovisual) attention-based motion, using stimuli composed of interleaved visual and auditory cues. Although subjects were able to track a trajectory using cues from both modalities, no one spontaneously perceived (“multimodal motion”) across both visual and auditory cues. Rather, they reported motion perception only within each modality, thereby revealing a spatiotemporal limit on putative cross-modal motion integration. Together, results from these experiments demonstrate the existence of attention-based motion in audition, extending current theories of attention-based mechanisms from visual to auditory systems.

Optogenetics is rapidly gaining acceptance as a preferred method to study specific neuronal cell types using light. Optogenetic neuromodulation requires the introduction of a cell-specific viral vector encoding for a light activating ion channel or ion pump and the utilization of a system to deliver light stimulation to brain. Here, we describe a two-part methodology starting with a procedure to inject an optogenetic AAV virus into rat cortex followed by a second procedure to surgically implant an optical cannula for light delivery to the deeper cortical layers.

Background: Multiple neurological disorders including Alzheimer’s disease (AD), mesial temporal sclerosis, and mild traumatic brain injury manifest with volume loss on brain MRI. Subtle volume loss is particularly seen early in AD. While prior research has demonstrated the value of this additional information from quantitative neuroimaging, very few applications have been approved for clinical use. Here we describe a US FDA cleared software program, NeuroreaderTM, for assessment of clinical hippocampal volume on brain MRI. Objective: To present the validation of hippocampal volumetrics on a clinical software program. Method: Subjects were drawn (n = 99) from the Alzheimer Disease Neuroimaging Initiative study. Volumetric brain MR imaging was acquired in both 1.5 T (n = 59) and 3.0 T (n = 40) scanners in participants with manual hippocampal segmentation. Fully automated hippocampal segmentation and measurement was done using a multiple atlas approach. The Dice Similarity Coefficient (DSC) measured the level of spatial overlap between NeuroreaderTM and gold standard manual segmentation from 0 to 1 with 0 denoting no overlap and 1 representing complete agreement. DSC comparisons between 1.5 T and 3.0 T scanners were done using standard independent samples T-tests. Results: In the bilateral hippocampus, mean DSC was 0.87 with a range of 0.78–0.91 (right hippocampus) and 0.76–0.91 (left hippocampus). Automated segmentation agreement with manual segmentation was essentially equivalent at 1.5 T (DSC = 0.879) versus 3.0 T (DSC = 0.872). Conclusion: This work provides a description and validation of a software program that can be applied in measuring hippocampal volume, a biomarker that is frequently abnormal in AD and other neurological disorders.

Functional magnetic resonance imaging (fMRI) is used clinically to map the visual cortex before brain surgery or other invasive treatments to achieve an optimal balance between therapeutic effect and the avoidance of postoperative vision deficits. Clinically optimized stimuli, analyses, and displays permit identification of cortical subregions supporting high-acuity central vision that are critical for reading and other essential visual functions. A novel data display permits instant appreciation of the functional relationship between the pattern of fMRI brain activation and the pattern of vision loss and preservation within the patient's field of view. Neurovascular uncoupling and its detection in the visual cortex are key issues for the interpretation of fMRI results in patients with existing brain pathology.

The sensorimotor system of the human brain and body is fundamental only in its central role in our daily lives. On further examination, it is a system with intricate and complex anatomical, physiological, and functional relationships. Sensorimotor areas including primary sensorimotor, premotor, supplementary motor, and higher order somatosensory cortices are critical for function and can be localized at routine neuroimaging with a familiarity of sulcal and gyral landmarks. Likewise, a thorough understanding of the functions and dysfunctions of these areas can empower the neuroradiologist and lead to superior imaging search patterns, diagnostic considerations, and patient care recommendations in daily clinical practice. Presurgical functional brain mapping of the sensorimotor system may be necessary in scenarios with distortion of anatomical landmarks, multiplanar localization, homunculus localization, congenital brain anomalies, informing diffusion tensor imaging interpretations, and localizing nonvisible targets.

The spatial topography of visual attention is a distinguishing and critical feature of many theoretical models of visuospatial attention. Previous fMRI-based measurements of the topography of attention have typically been too crude to adequately test the predictions of different competing models. This study demonstrates a new technique to make detailed measurements of the topography of visuospatial attention from single-voxel, fMRI time courses. Briefly, this technique involves first estimating a voxel's population receptive field (pRF) and then “drifting” attention through the pRF such that the modulation of the voxel's fMRI time course reflects the spatial topography of attention. The topography of the attentional field (AF) is then estimated using a time-course modeling procedure. Notably, we are able to make these measurements in many visual areas including smaller, higher order areas, thus enabling a more comprehensive comparison of attentional mechanisms throughout the full hierarchy of human visual cortex. Using this technique, we show that the AF scales with eccentricity and varies across visual areas. We also show that voxels in multiple visual areas exhibit suppressive attentional effects that are well modeled by an AF having an enhancing Gaussian center with a suppressive surround. These findings provide extensive, quantitative neurophysiological data for use in modeling the psychological effects of visuospatial attention.

Macaques indicated their detection of onset or alteration of 0.2-ms pulses applied in various configurations through electrodes implanted in striate cortex. When microelectrodes were introduced and left in place, the threshold for detection of 100-Hz pulses nearly doubled within 24 h. However, for chronically implanted platinum-alloy macroelectrodes detection thresholds usually remained stable for many months, independently of location within striate cortex or its immediately subjacent white matter. Thresholds were unaffected by the visual conditions, such as light versus darkness, or movement of the eyes; but in one animal blind after acute glaucoma thresholds for loci in striate cortex were permanently decreased by about 50%. Learning to respond to electrical stimulation of the optic tract produced no tendency to respond to such stimulation of striate cortex. Onset of stimulation at a given locus could be detected even in the face of continuous supraliminal stimulation at four surrounding loci on a 3-mm radius. The surround stimulation did alter the threshold of the central locus, but such stimuli could not summate if they were subliminal by some 10%. Cessation of stimulation that had been continuing for 1 min to 1 h could be detected if it were being applied at a level 20–75% above that needed for detection of stimulus onset. Continuous stimulation had a pronounced “priming” effect, in that modulation of frequency or intensity of such stimulation by as little as 5% could be detected (e.g., 20 μA in a background of 500 μA, or

We present an efficient algorithm using the Hilbert Transform for estimating the delay of the BOLD response to neuronal stimulation. With minimal additional computations, the algorithm estimates parameters generated in the widely used cross-correlation method and simplifies the interpolation required to estimate the response delay from the cross-correlation function. We examined errors in the Hilbert-based delay estimate associated with the use of DFT on short-duration discrete signals and proposed a method for minimizing these errors. Furthermore, we compared the delay estimates obtained with the Hilbert method to those obtained using the onset of the BOLD response. The Hilbert method resulted in less variance in the delay estimate despite the potential for higher variability in the latter part of the BOLD response. This improved delay estimate was attributed to the reduced sensitivity of the Hilbert method to noise contamination compared to the onset method.

Functional magnetic resonance imaging (fMRI) is used clinically to map visual cortex prior to brain surgery or other invasive treatments in order to achieve an optimal balance between therapeutic effect and the avoidance of post-operative vision deficits. Clinically optimized stimuli, behavioral task, analysis and displays permit identification of cortical subregions supporting high acuity central vision that is critical for reading and other essential visual functions. A novel data display permits instant appreciation of the functional relationship between the pattern of fMRI brain activation and the pattern of vision loss and preservation within the patient’s field of view. Neurovascular uncoupling and its detection in visual cortex are key issues for the interpretation of fMRI results in patients with existing brain pathology. Emerging techniques such as resting state fMRI may facilitate the use of fMRI-based vision mapping with a broader range of patients.

Preoperative mapping has revolutionized neurosurgical care for brain tumor patients. Maximizing resections has improved diagnosis, optimized treatment algorithms, and decreased potentially devastating postoperative deficits. Although mapping has multiple steps and complimentary localization sources, diffusion tensor imaging (DTI) excels in its essential role in depicting white matter tracts. A thorough understanding of DTI, data visualization methods, and limitations with mastery of functional and dysfunctional white matter anatomy is necessary to realize the potential of DTI. By establishing spatial relationships between lesion borders and functional networks preoperatively and intraoperatively, DTI is central to high-risk neurosurgical resections and becoming the standard of care.

The Parahippocampal Place Area (PPA; Epstein & Kanwisher, 1998) is a region within posterior parahippocampal cortex that responds selectively to visual stimuli that convey information about the layout of local space. Here we describe two patients who suffered damage to the PPA after vascular incidents. Both subsequently exhibited memory problems for topographical materials and were unable to navigate unassisted in unfamiliar environments. Performance on a continuous n-back visual memory test was significantly lower for novel scene-like stimuli than for novel object-like stimuli. In contrast, performance was normal on a famous landmark recognition task and on two perceptual tasks that required on-line analysis of scene geometry. Both patients were able to produce accurate maps of premorbidly learned places but were unable to produce accurate maps of new places. These results converge with previous neuroimaging work to demonstrate that the PPA (1) is selectively involved in processing information about the geometry of surrounding space, and (2) may play a more critical role in the encoding of this information into memory than in the initial perceptual processing, recognition, or recall of this information.

Evidence from imaging studies suggests that primary visual cortex and multiple areas in ventral occipitotemporal cortex subserve color perception in humans. To learn more about the organization of these areas, we used structural and functional MRI (fMRI) to examine a patient with damage to ventral cortex. An art professor, KG, suAered a cerebrovascular accident during heart surgery that impaired his ability to perceive color. The Farnsworth‐Munsell 100-Hue test was used to assess the extent of his deficit. When tested 12 months after the lesion, KG performed worse than 95% of age-matched normals on the 100-Hue test, but well above chance. Structural and functional MRI studies were conducted 3 years after the lesion to investigate the neuroanatomical correlates of KG’ss remaining color ability. Structural MRI revealed bilateral damage to ventral occipitotemporal cortex. In young and age-matched normal controls, an fMRI version of the 100-Hue reliably activated bilateral, color-selective regions in primary visual cortex and anterior and posterior ventral cortex. In subject KG, color-selective cortex was found in bilateral primary visual cortex. In ventral cortex, no color-selective activity was observed in right ventral cortex, and only a small area of activity was observed in left anterior ventral cortex. However, significant color-selective activity was observed in posterior left ventral cortex spared by the lesion. This posterior left ventral activation was similar in extent, position, and degree of color-selectivity to the posterior left posterior activation observed in normal controls, suggesting that this focus may be the cortical substrate underlying KG’s remaining color perception. Published by Elsevier Science Ltd.

Studies of patients with cerebral achromatopsia have suggested that ventral occipitotemporal cortex is important for color perception. We created a functional magnetic resonance imaging (fMRI) version of a clinical test commonly used to assess achromatopsia, the Farnsworth-Munsell 100-Hue test. The test required normal subjects to use color information in the visual stimulus to perform a color sequencing task. A modification of the test requiring ordering by luminance was used as a control task. Subjects were also imaged as they passively viewed colored stimuli. A limited number of areas responded more to chromatic than achromatic stimulation, including primary visual cortex. Most color-selective activity was concentrated in ventral occipitotemporal cortex. Several areas in ventral cortex were identified. The most posterior, located in posterior fusiform gyrus, corresponded to the area activated by passive viewing of colored stimuli. More anterior and medial color-selective areas were located in the collateral sulcus and fusiform gyrus. These more anterior areas were not identified in previous imaging studies which used passive viewing of colored stimuli, and were most active in our study when visual color information was behaviorally relevant, suggesting that attention influences activity in color-selective areas. The fMRI version of the Farnsworth-Munsell test may be useful in the study of achromatopsia.

Beauchamp, Michael S., Robert W. Cox, and Edgar A. DeYoe. Graded effects of spatial and featural attention on human area MT and associated motion processing areas. J. Neurophysiol. 78: 516–520, 1997. Functional magnetic resonance imaging was used to quantify the effects of changes in spatial and featural attention on brain activity in the middle temporal visual area and associated motion processing regions (hMT+) of normal human subjects. When subjects performed a discrimination task that directed their spatial attention to a peripherally presented annulus and their featural attention to the speed of points in the annulus, activity in hMT+ was maximal. If subjects were instead asked to discriminate the color of points in the annulus, the magnitude and volume of activation in hMT+ fell to 64 and 35%, respectively, of the previously observed maximum response. In another experiment, subjects were asked to direct their spatial attention away from the annulus toward the fixation point to detect a subtle change in luminance. The response magnitude and volume dropped to 40 and 9% of maximum. These experiments demonstrate that both spatial and featural attention modulate hMT+ and that their effects can work in concert to modulate cortical activity. The high degree of modulation by attention suggests that an understanding of the stimulus-driven properties of visual cortex needs to be complemented with an investigation of the effects of task-related factors on visual processing.

It remains unclear to what extent retinotopic maps can undergo large-scale plasticity following damage to human visual cortex. The literature has predominately focused on retinotopic changes in patients with retinal pathologies or congenital brain malformations. Yet, damage to the adult visual cortex itself is common in cases such as stroke, tumor, or trauma. To address this issue, we used a unique database of fMRI vision maps in patients with adult-onset (n = 25) and congenital (n = 2) pathology of the visual cortex. We identified atypical retinotopic organization in three patients (two with adult-onset, and one with congenital pathology) consisting of an expanded ipsilateral field representation that was on average 3.2 times greater than healthy controls. The expanded representations were located at the vertical meridian borders between visual areas such as V1/V2. Additionally, two of the three patients had apparently an ectopic (topographically inconsistent) representation of the ipsilateral field within lateral occipital cortex that is normally associated with visual areas V3/V3A (and possibly other areas). Both adult-onset cases had direct damage to early visual cortex itself (rather than to the afferent drive only), resulting in a mostly nonfunctional hemisphere. The congenital case had severe cortical malformation of the visual cortex and was acallosal. Our results are consistent with a competitive model in which unilateral damage to visual cortex or disruption of the transcallosal connections removes interhemispheric suppression from retino-geniculate afferents in intact visual cortex that represent the vertical meridian and ipsilateral visual field.

Data obtained from functional magnetic resonance imaging are often limited by a low signal-to-noise ratio. The time-course data obtained from activated regions contain both system noise and physiological noise, primarily linked to the heart and respiratory rates, that are superimposed on task induced signals. Time averaging of a practical number of data sets is not very effective in improving the signal-to-noise ratio because neither system nor physiological noise is truly random. In this paper, a method is presented for filtering unwanted physiological fluctuations, including aliased signals that are formed as a result of long repetition time (TR) values. A pulse oximeter was used to obtain cardiac and respiratory information during the scanning period. Finite impulse response band-reject digital filters were designed to remove the physiological fluctuations. For comparison, cross-correlation analyses were performed at the same level of statistical significance on both filtered and unfiltered data. We demonstrate that this method can improve the detection of weak signals without increasing the probability of false positives.

To determine if changes in metabolic capacity revealed by cytochrome oxidase (CO) histochemistry are related to sustained changes in energy-utilizing neuronal activity, we assayed CO levels and recorded multiunit firing rates along nearly tangential penetrations of V1 in seven adult macaque monkeys before and after single, monocular injections of TTX. Within as little as 14 h, TTX blockade began to reduce CO staining in zones of layer 4C that received dominant input from the injected eye. Since simple monocular occlusion has only minor effects on cortical CO levels (Trusk et al., 1990), the changes in activity that were specifically associated with CO depletion were isolated by comparing spike rates during monocular TTX blockade and during monocular occlusion. Five second samples of multiunit spike rate were obtained after 2-min adaptation to each of four adapting fields: black, gray, white, and textured. Results were similar for these four conditions. In layer 4C, ocular dominance zones with input from the TTX eye had ongoing spike rates that were 48% of the rates in zones with input from a normal but occluded eye. In six animals, it was possible to record activity at a single site before, during, and after the onset of TTX blockade. Background activity at these interpuff sites decreased as much as 3-fold in less than 1 h but stabilized within 3–4 h to an average of 53% of pre-TTX rates. These data support the interpretation that energy utilization linked to sustained spike rates partially regulates CO levels under normal conditions, at least in layer 4. Furthermore, changes in neuronal activity induced by retinal TTX preceded the detectable reduction in CO activity in V1 suggesting that the adjustment of CO levels was in response to the altered activity.

Functional magnetic resonance imaging (FMRI) can provide detailed images of human brain that reflect localized changes in cerebral blood flow and oxygenation induced by sensory, motor, or cognitive tasks. This review presents methods for gradient-recalled echo-planar functional magnetic resonance imaging (FMRI). Also included is a discussion of the hypothesized basis of FMRI, imaging hardware, a unique visual stimulation apparatus, image post-processing and statistical analysis. Retinotopic mapping of striate and extrastriate visual cortex is discussed as an example application. The described echo-planar technique permitted acquisition of an image in 40 ms with a repetition rate of up to 2 per second. However, FMRI responses are slow compared to changes in neural activity. Onset of a visual checkerboard test pattern evoked a response that was delayed by 1–2 s and reached 90% of peak in 5 s. Return to baseline following stimulation was slightly slower. Alternating control (blank) and test (checkerboard) patterns every 20 s induced a cyclic response that was detected in the presence of noise using a cross-correlation technique that was verified by parametric statistics. FMRI revealed retinotopically organized patterns of visually evoked activity in response to annular stimuli that increased in visual field eccentricity. Retinotopy was also observed with test patterns rotated around the fixation point (center of gaze). Results from repeated tests 1 week apart were highly similar. Compared to passive viewing, an active visual discrimination task enhanced responses from extrastriate association cortex.