Maps of the Auditory Cortex.

One of the fundamental properties of the mammalian brain is that sensory regions of cortex are formed of multiple, functionally specialized cortical field maps (CFMs). Each CFM comprises two orthogonal topographical representations, reflecting two essential aspects of sensory space. In auditory cortex, auditory field maps (AFMs) are defined by the combination of tonotopic gradients, representing the spectral aspects of sound (i.e., tones), with orthogonal periodotopic gradients, representing the temporal aspects of sound (i.e., period or temporal envelope). Converging evidence from cytoarchitectural and neuroimaging measurements underlies the definition of 11 AFMs across core and belt regions of human auditory cortex, with likely homology to those of macaque. On a macrostructural level, AFMs are grouped into cloverleaf clusters, an organizational structure also seen in visual cortex. Future research can now use these AFMs to investigate specific stages of auditory processing, key for understanding behaviors such as speech perception and multimodal sensory integration.

fMRI of the rod scotoma elucidates cortical rod pathways and implications for lesion measurements.

Are silencing, ectopic shifts, and receptive field (RF) scaling in cortical scotoma projection zones (SPZs) the result of long-term reorganization (plasticity) or short-term adaptation? Electrophysiological studies of SPZs after retinal lesions in animal models remain controversial, because they are unable to conclusively answer this question because of limitations of the methodology. Here, we used functional MRI (fMRI) visual field mapping through population RF (pRF) modeling with moving bar stimuli under photopic and scotopic conditions to measure the effects of the rod scotoma in human early visual cortex. As a naturally occurring central scotoma, it has a large cortical representation, is free of traumatic lesion complications, is completely reversible, and has not reorganized under normal conditions (but can as seen in rod monochromats). We found that the pRFs overlapping the SPZ in V1, V2, V3, hV4, and VO-1 generally (i) reduced their blood oxygen level-dependent signal coherence and (ii) shifted their pRFs more eccentric but (iii) scaled their pRF sizes in variable ways. Thus, silencing, ectopic shifts, and pRF scaling in SPZs are not unique identifiers of cortical reorganization; rather, they can be the expected result of short-term adaptation. However, are there differences between rod and cone signals in V1, V2, V3, hV4, and VO-1? We did not find differences for all five maps in more peripheral eccentricities outside of rod scotoma influence in coherence, eccentricity representation, or pRF size. Thus, rod and cone signals seem to be processed similarly in cortex.

A lack of experience-dependent plasticity after more than a decade of recovered sight.

In 2000, monocular vision was restored to M. M., who had been blind between the ages of 3 and 46 years. Tests carried out over 2 years following the surgery revealed impairments of 3-D form, object, and face processing and an absence of object- and face-selective blood-oxygen-level-dependent responses in ventral visual cortex. In the present research, we reexamined M. M. to test for experience-dependent recovery of visual function. Behaviorally, M. M. remains impaired in 3-D form, object, and face processing. Accordingly, we found little to no evidence of the category-selective organization within ventral visual cortex typically associated with face, body, scene, or object processing. We did observe remarkably normal object selectivity within lateral occipital cortex, consistent with M. M.'s previously reported shape-discrimination performance. Together, these findings provide little evidence for recovery of high-level visual function after more than a decade of visual experience in adulthood.

Orthogonal acoustic dimensions define auditory field maps in human cortex.

The functional organization of human auditory cortex has not yet been characterized beyond a rudimentary level of detail. Here, we use functional MRI to measure the microstructure of orthogonal tonotopic and periodotopic gradients forming complete auditory field maps (AFMs) in human core and belt auditory cortex. These AFMs show clear homologies to subfields of auditory cortex identified in nonhuman primates and in human cytoarchitectural studies. In addition, we present measurements of the macrostructural organization of these AFMs into "clover leaf" clusters, consistent with the macrostructural organization seen across human visual cortex. As auditory cortex is at the interface between peripheral hearing and central processes, improved understanding of the organization of this system could open the door to a better understanding of the transformation from auditory spectrotemporal signals to higher-order information such as speech categories.

Paradoxical visuomotor adaptation to reversed visual input is predicted by BDNF Val66Met polymorphism.

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the brain, influencing neural development, plasticity, and repair (Chen et al., 2004; Thoenen, 1995). The BDNF gene contains a single-nucleotide polymorphism (SNP) called Val(66)Met. The Met allele interferes with intracellular BDNF-trafficking, decreases activity-dependent BDNF secretion, and consequently is often associated with a shift from plasticity to stability in neural circuits (Egan et al., 2003). We investigated the behavioral consequences of the presence of the Met allele by comparing how 40 heterozygous subjects with the Val/Met genotype and 35 homozygous subjects with the Val/Val genotype performed on visuomotor tasks (reaching and navigation) under two conditions: normal vision and completely left-right reversed vision. As expected, subjects did not differ in their short-term ability to learn the tasks with normal vision (p = 0.58). Intuitively, it would be expected that homozygous Val/Val subjects with a propensity for greater BDNF-induced activity-dependent plasticity would learn new tasks more quickly than heterozygous Val/Met subjects with decreased BDNF secretion (Gilbert, Li, & Piech, 2009). However, we found the opposite here. When short-term mechanisms of visuomotor adaptation were engaged to compensate for the misalignment of visual and somatomotor information created by the left-right reversal of vision, heterozygous Val/Met subjects learned significantly more quickly than their homozygous Val/Val counterparts (p = 0.027). Our results demonstrate the paradoxical finding that the presence of the Met allele, which is thought to promote cortical stability, here improves immediate visuomotor adaptation to left-right-reversed visual input.

Cortical field maps across human sensory cortex.

Cortical processing pathways for sensory information in the mammalian brain tend to be organized into topographical representations that encode various fundamental sensory dimensions. Numerous laboratories have now shown how these representations are organized into numerous cortical field maps (CMFs) across visual and auditory cortex, with each CFM supporting a specialized computation or set of computations that underlie the associated perceptual behaviors. An individual CFM is defined by two orthogonal topographical gradients that reflect two essential aspects of feature space for that sense. Multiple adjacent CFMs are then organized across visual and auditory cortex into macrostructural patterns termed cloverleaf clusters. CFMs within cloverleaf clusters are thought to share properties such as receptive field distribution, cortical magnification, and processing specialization. Recent measurements point to the likely existence of CFMs in the other senses, as well, with topographical representations of at least one sensory dimension demonstrated in somatosensory, gustatory, and possibly olfactory cortical pathways. Here we discuss the evidence for CFM and cloverleaf cluster organization across human sensory cortex as well as approaches used to identify such organizational patterns. Knowledge of how these topographical representations are organized across cortex provides us with insight into how our conscious perceptions are created from our basic sensory inputs. In addition, studying how these representations change during development, trauma, and disease serves as an important tool for developing improvements in clinical therapies and rehabilitation for sensory deficits.

Visual field maps in human cortex.

Much of the visual cortex is organized into visual field maps: nearby neurons have receptive fields at nearby locations in the image. Mammalian species generally have multiple visual field maps with each species having similar, but not identical, maps. The introduction of functional magnetic resonance imaging made it possible to identify visual field maps in human cortex, including several near (1) medial occipital (V1,V2,V3), (2) lateral occipital (LO-1,LO-2, hMT+), (3) ventral occipital (hV4, VO-1, VO-2), (4) dorsal occipital (V3A, V3B), and (5) posterior parietal cortex (IPS-0 to IPS-4). Evidence is accumulating for additional maps, including some in the frontal lobe. Cortical maps are arranged into clusters in which several maps have parallel eccentricity representations, while the angular representations within a cluster alternate in visual field sign. Visual field maps have been linked to functional and perceptual properties of the visual system at various spatial scales, ranging from the level of individual maps to map clusters to dorsal-ventral streams. We survey recent measurements of human visual field maps, describe hypotheses about the function and relationships between maps, and consider methods to improve map measurements and characterize the response properties of neurons comprising these maps.

Lack of long-term cortical reorganization after macaque retinal lesions.

Several aspects of cortical organization are thought to remain plastic into adulthood, allowing cortical sensorimotor maps to be modified continuously by experience. This dynamic nature of cortical circuitry is important for learning, as well as for repair after injury to the nervous system. Electrophysiology studies suggest that adult macaque primary visual cortex (V1) undergoes large-scale reorganization within a few months after retinal lesioning, but this issue has not been conclusively settled. Here we applied the technique of functional magnetic resonance imaging (fMRI) to detect changes in the cortical topography of macaque area V1 after binocular retinal lesions. fMRI allows non-invasive, in vivo, long-term monitoring of cortical activity with a wide field of view, sampling signals from multiple neurons per unit cortical area. We show that, in contrast with previous studies, adult macaque V1 does not approach normal responsivity during 7.5 months of follow-up after retinal lesions, and its topography does not change. Electrophysiology experiments corroborated the fMRI results. This indicates that adult macaque V1 has limited potential for reorganization in the months following retinal injury.

Visual field maps and stimulus selectivity in human ventral occipital cortex.

Human visual cortex is organized into distinct visual field maps whose locations and properties provide important information about visual computations. There are two conflicting models of the organization and computational role of ventral occipital visual field maps. We report new functional MRI measurements that test these models. We also present the first coordinated measurements of visual field maps and stimulus responsivity to color, objects and faces in ventral occipital cortex. These measurements support a model that includes a hemifield map, hV4, adjacent to the central field representation of ventral V3. In addition, the measurements demonstrate a cluster of visual field maps in ventral occipital cortex (VO cluster) anterior to hV4. We describe the organization and stimulus responsivity of two new hemifield maps, VO-1 and VO-2, within this cluster. The maps and stimulus responsivity support a general organization of visual cortex based on clusters of maps that serve distinct computational functions.

Reorganization of human cortical maps caused by inherited photoreceptor abnormalities.

We describe a compelling demonstration of large-scale developmental reorganization in the human visual pathways. The developmental reorganization was observed in rod monochromats, a rare group of congenitally colorblind individuals who virtually lack cone photoreceptor function. Normal controls had a cortical region, spanning several square centimeters, that responded to signals initiated in the all-cone foveola but was inactive under rod viewing conditions; in rod monochromats this cortical region responded powerfully to rod-initiated signals. The measurements trace a causal pathway that begins with a genetic anomaly that directly influences sensory cells and ultimately results in a substantial central reorganization.

Visual Field Map Clusters in High-Order Visual Processing: Organization of V3A/V3B and a New Cloverleaf Cluster in the Posterior Superior Temporal Sulcus.

The cortical hierarchy of the human visual system has been shown to be organized around retinal spatial coordinates throughout much of low- and mid-level visual processing. These regions contain visual field maps (VFMs) that each follows the organization of the retina, with neighboring aspects of the visual field processed in neighboring cortical locations. On a larger, macrostructural scale, groups of such sensory cortical field maps (CFMs) in both the visual and auditory systems are organized into roughly circular cloverleaf clusters. CFMs within clusters tend to share properties such as receptive field distribution, cortical magnification, and processing specialization. Here we use fMRI and population receptive field (pRF) modeling to investigate the extent of VFM and cluster organization with an examination of higher-level visual processing in temporal cortex and compare these measurements to mid-level visual processing in dorsal occipital cortex. In human temporal cortex, the posterior superior temporal sulcus (pSTS) has been implicated in various neuroimaging studies as subserving higher-order vision, including face processing, biological motion perception, and multimodal audiovisual integration. In human dorsal occipital cortex, the transverse occipital sulcus (TOS) contains the V3A/B cluster, which comprises two VFMs subserving mid-level motion perception and visuospatial attention. For the first time, we present the organization of VFMs in pSTS in a cloverleaf cluster. This pSTS cluster contains four VFMs bilaterally: pSTS-1:4. We characterize these pSTS VFMs as relatively small at ∼125 mm2 with relatively large pRF sizes of ∼2-8° of visual angle across the central 10° of the visual field. V3A and V3B are ∼230 mm2 in surface area, with pRF sizes here similarly ∼1-8° of visual angle across the same region. In addition, cortical magnification measurements show that a larger extent of the pSTS VFM surface areas are devoted to the peripheral visual field than those in the V3A/B cluster. Reliability measurements of VFMs in pSTS and V3A/B reveal that these cloverleaf clusters are remarkably consistent and functionally differentiable. Our findings add to the growing number of measurements of widespread sensory CFMs organized into cloverleaf clusters, indicating that CFMs and cloverleaf clusters may both be fundamental organizing principles in cortical sensory processing.

Visual areas in macaque cortex measured using functional magnetic resonance imaging.

We describe the first systematic functional magnetic resonance imaging (fMRI) measurements of visual field maps in macaque visual cortex. The boundaries of visual areas V1, V2, V3, V3A, V4, MT/V5, and TEO/V4A were identified using stimuli that create traveling waves of activity in retinotopically organized areas of the visual cortex. Furthermore, these stimuli were used to measure the dimensions of the representations of the central 11 degrees in V1-V3, quantitative visual field eccentricity functions for V1-V3 and MT, and the distribution of foveal and peripheral signals within the occipital lobe. Within areas V1, V2, MT, and portions of V4, the fMRI signals were 5-10 times the noise level (3 mm3 volumes of interest). Signals were weaker but still significant in other cortical regions, including V3, V3A, and TEO. There is good agreement between the fMRI maps and the visual area maps discovered using local anatomical and physiological measurements. The fMRI measurements allow one to obtain a broad view of the distribution of cortical signals, spanning multiple visual areas at a single point in time. The combination of scale and sensitivity demonstrated here create a good foundation for measuring how localized signals and lesions influence the responses and reorganization in widely separated cortical regions. The ability to measure human and macaque maps using the same technology will make it possible to define computational homologies between the two species.

Visual field representations and locations of visual areas V1/2/3 in human visual cortex.

The position, surface area and visual field representation of human visual areas V1, V2 and V3 were measured using fMRI in 7 subjects (14 hemispheres). Cortical visual field maps of the central 12 deg were measured using rotating wedge and expanding ring stimuli. The boundaries between areas were identified using an automated procedure to fit an atlas of the expected visual field map to the data. All position and surface area measurements were made along the boundary between white matter and gray matter. The representation of the central 2 deg of visual field in areas V1, V2, V3 and hV4 spans about 2100 mm2 and is centered on the lateral-ventral aspect of the occipital lobes at Talairach coordinates -29, -78, -11 and 25, -80, -9. The mean area between the 2-deg and 12-deg eccentricities for the primary visual areas was: V1: 1470 mm2; V2: 1115 mm2; and V3: 819 mm2. The sizes of areas V1, V2 and V3 varied by about a factor of 2.5 across individuals; the sizes of V1 and V2 are significantly correlated within individuals, but there is a very low correlation between V1 and V3. These in vivo measurements of normal human retinotopic visual areas can be used as a reference for comparison to unusual cases involving developmental plasticity, recovery from injury, identifying homology with animal models, or analyzing the computational resources available within the visual pathways.

Visual cortex in aging and Alzheimer's disease: changes in visual field maps and population receptive fields.

Although several studies have suggested that cortical alterations underlie such age-related visual deficits as decreased acuity, little is known about what changes actually occur in visual cortex during healthy aging. Two recent studies showed changes in primary visual cortex (V1) during normal aging; however, no studies have characterized the effects of aging on visual cortex beyond V1, important measurements both for understanding the aging process and for comparison to changes in age-related diseases. Similarly, there is almost no information about changes in visual cortex in Alzheimer's disease (AD), the most common form of dementia. Because visual deficits are often reported as one of the first symptoms of AD, measurements of such changes in the visual cortex of AD patients might improve our understanding of how the visual system is affected by neurodegeneration as well as aid early detection, accurate diagnosis and timely treatment of AD. Here we use fMRI to first compare the visual field map (VFM) organization and population receptive fields (pRFs) between young adults and healthy aging subjects for occipital VFMs V1, V2, V3, and hV4. Healthy aging subjects do not show major VFM organizational deficits, but do have reduced surface area and increased pRF sizes in the foveal representations of V1, V2, and hV4 relative to healthy young control subjects. These measurements are consistent with behavioral deficits seen in healthy aging. We then demonstrate the feasibility and first characterization of these measurements in two patients with mild AD, which reveal potential changes in visual cortex as part of the pathophysiology of AD. Our data aid in our understanding of the changes in the visual processing pathways in normal aging and provide the foundation for future research into earlier and more definitive detection of AD.

Visual Working Memory in Human Cortex.

Visual working memory (VWM) is the ability to maintain visual information in a readily available and easily updated state. Converging evidence has revealed that VWM capacity is limited by the number of maintained objects, which is about 3 - 4 for the average human. Recent work suggests that VWM capacity is also limited by the resolution required to maintain objects, which is tied to the objects' inherent complexity. Electroencephalogram (EEG) studies using the Contralateral Delay Activity (CDA) paradigm have revealed that cortical representations of VWM are at a minimum loosely organized like the primary visual system, such that the left side of space is represented in the right hemisphere, and vice versa. Recent functional magnetic resonance imaging (fMRI) work shows that the number of objects is maintained by representations in the inferior intraparietal sulcus (IPS) along dorsal parietal cortex, whereas the resolution of these maintained objects is subserved by the superior IPS and the lateral occipital complex (LOC). These areas overlap with recently-discovered, retinotopically-organized visual field maps (VFMs) spanning the IPS (IPS-0/1/2/3/4/5), and potentially maps in lateral occipital cortex, such as LO-1/2, and/or TO-1/2 (hMT+). Other fMRI studies have implicated early VFMs in posterior occipital cortex, suggesting that visual areas V1-hV4 are recruited to represent information in VWM. Insight into whether and how these VFMs subserve VWM may illuminate the nature of VWM. In addition, understanding the nature of these maps may allow a greater investigation into individual differences among subjects and even between hemispheres within subjects.

A dynamic, embodied paradigm to investigate the role of serotonin in decision-making.

Serotonin (5-HT) is a neuromodulator that has been attributed to cost assessment and harm aversion. In this review, we look at the role 5-HT plays in making decisions when subjects are faced with potential harmful or costly outcomes. We review approaches for examining the serotonergic system in decision-making. We introduce our group's paradigm used to investigate how 5-HT affects decision-making. In particular, our paradigm combines techniques from computational neuroscience, socioeconomic game theory, human-robot interaction, and Bayesian statistics. We will highlight key findings from our previous studies utilizing this paradigm, which helped expand our understanding of 5-HT's effect on decision-making in relation to cost assessment. Lastly, we propose a cyclic multidisciplinary approach that may aid in addressing the complexity of exploring 5-HT and decision-making by iteratively updating our assumptions and models of the serotonergic system through exhaustive experimentation.

Effects of healthy aging on human primary visual cortex.

Aging often results in reduced visual acuity from changes in both the eye and neural circuits [1-4]. In normally aging subjects, primary visual cortex has been shown to have reduced responses to visual stimulation [5]. It is not known, however, to what extent aging affects visual field representations and population receptive sizes in human primary visual cortex. Here we use functional MRI (fMRI) and population receptive field (pRF) modeling [6] to measure angular and eccentric retinotopic representations and population receptive fields in primary visual cortex in healthy aging subjects ages 57 - 70 and in healthy young volunteers ages 24 - 36 (n = 9). Retinotopic stimuli consisted of black and white, drifting checkerboards comprising moving bars 11 deg in radius. Primary visual cortex (V1) was clearly identifiable along the calcarine sulcus in all hemispheres. There was a significant decrease in the surface area of V1 from 0 to 3 deg eccentricity in the aging subjects with respect to the young subjects (p = 0.039). The coherence of the fMRI% BOLD modulation was significantly decreased in the aging subjects compared to the young subjects in the more peripheral eccentricity band from 7 to 10 deg (p = 0.029). Finally, pRF sizes were significantly increased within the 0 to 3 deg foveal representation of V1 in the aging subjects compared to the young subjects (p = 0.019). Understanding the extent of changes that occur in primary visual cortex during normal aging is essential both for understanding the normal aging process and for comparisons of healthy, aging subjects with aging patients suffering from age-related visual and cortical disorders.

Visual maps: To merge or not to merge.

A recent study of a child born with one cerebral hemisphere has revealed an extreme developmental reorganization of visual cortex. Self-organizing visual maps demonstrate a surprisingly flexible restructuring in response to cortical loss.

Visual field map clusters in human cortex.

We describe the location and general properties of nine human visual field maps. The cortical location of each map, as well as many examples of the eccentricity and angular representations within these maps, are shown in a series of images that summarize a large set of functional MRI data. The organization and properties of these maps are compared and contrasted with descriptions by other investigators. We hypothesize that the human visual field maps are arranged in several clusters, each comprising a group of maps that share a common foveal representation and semicircular eccentricity map. The spatial organization of these clusters suggests that the perceptual processing within each cluster serves related functions.