Eve De Rosa

Opposing Influences of Affective State Valence on Visual Cortical Encoding

Positive and negative emotional states are thought to have originated from fundamentally opposing approach and avoidance behaviors. Furthermore, affective valence has been hypothesized to exert opposing biases in cognitive control. Here we examined with functional magnetic resonance imaging whether the opposing influences of positive and negative states extend to perceptual encoding in the visual cortices. Based on prior behavioral research, we hypothesized that positive states would broaden and negative states would narrow visual field of view (FOV). Positive, neutral, and negative states were induced on alternating blocks. To index FOV, observers then viewed brief presentations (300 ms) of face/place concentric center/surround stimuli on interleaved blocks. Central faces were attended, rendering the place surrounds unattended. As face and place information was presented at different visual eccentricities, our physiological metric of FOV was a valence-dependent modulation of place processing in the parahippocampal place area (PPA). Consistent with our hypotheses, positive affective states increased and negative states decreased PPA response to novel places as well as adaptation to repeated places. Individual differences in self-reported positive and negative affect correlated inversely with PPA encoding of peripheral places, as well as with activation in the mesocortical prefrontal cortex and amygdala. Psychophysiological interaction analyses further demonstrated that valence-dependent responses in the PPA arose from opponent coupling with extrafoveal regions of the primary visual cortex during positive and negative states. These findings collectively suggest that affective valence differentially biases gating of early visual inputs, fundamentally altering the scope of perceptual encoding.

Striatal and forebrain nuclei volumes: Contribution to motor function and working memory deficits in alcoholism

BACKGROUND Striatal structures are involved in dopaminergic alcohol reward mechanisms and aspects of motor control. Basal forebrain structures hold cholinergic mechanisms influencing memory formation, vulnerable to chronic alcoholism; however, alcoholisms effect on volumes of these structures has seldom been considered with in vivo measurement. METHODS We measured bilateral volumes of caudate nucleus, putamen, nucleus accumbens, and medial septal/diagonal band (MS/DB) in 25 men with alcohol dependence and 51 age-matched control men. Six alcoholic subjects had been drinking recently, and 19 had been sober. RESULTS Volumes of caudate and putamen were smaller in the alcoholics than in the control subjects, regardless of length of sobriety. Recent drinkers showed greater deficits in nucleus accumbens than sober alcoholics. Putamen volume was positively correlated with grip strength; MS/DB volume was positively correlated with verbal working memory independently of the negative association between age-standardized MS/DB and age in alcoholics. CONCLUSIONS Caudate and putamen volume deficits occur and endure in chronic alcoholism. Nucleus accumbens might be especially sensitive to recent alcohol exposure. Striatal volumes should be considered in functional imaging studies of alcohol craving that target striatal brain regions. The age-alcohol interaction for MS/DB volumes is consistent with a cholinergic mechanism for the working memory impairment observed in the alcoholics.

Cholinergic deafferentation of the neocortex using 192 IgG-saporin impairs feature binding in rats.

The binding problem refers to the fundamental challenge of the CNS to integrate sensory information registered by distinct brain regions to form a unified neural representation of a stimulus. Although the human cognitive literature has established that attentional processes in frontoparietal cortices support feature binding, the neurochemical and specific downstream neuroanatomical contributions to feature binding remain unknown. Using systemic pharmacology in rats, it has been shown that the neuromodulator acetylcholine is essential for feature binding at encoding, but the neural source of such critical cholinergic neurotransmission has yet to be identified. Cholinergic efferents from the nucleus basalis magnocellularis (NBM) of the basal forebrain provide the majority of the cholinergic input to the neocortex. Accordingly, it was hypothesized that the NBM is the neural source that provides the critical neuromodulatory support for feature binding. To test this hypothesis, rats received bilateral 192 IgG-saporin lesions of the NBM, and their feature binding performance was tested using a forced-choice digging paradigm. Relative to sham-lesioned rats, NBM-lesioned rats were significantly impaired at acquiring a crossmodal feature conjunction (FC) stimulus set that required feature binding, whereas their ability to retrieve an FC stimulus set and to acquire two crossmodal feature singleton stimulus sets, one of greater difficulty than the other but neither requiring feature binding, remained intact. These behavioral findings, along with histological analyses demonstrating positive relationships between feature-binding acquisition and markers of cholinergic activity in frontoparietal regions, reveal the importance of neocortical cholinergic input from the NBM to feature binding at encoding.

Cholinergic Influences on Feature Binding

The binding problem refers to the fundamental challenge of the central nervous system to integrate sensory information registered by multiple brain regions to form a unified neural representation of a stimulus. Human behavioral, neuropsychological, and functional neuroimaging evidence suggests a fundamental role for attention in feature binding; however, its neurochemical basis is currently unknown. This study examined whether acetylcholine (ACh), a neuromodulator that has been implicated in attentional processes, plays a critical role in feature binding. Using a within-subjects pharmacological design and the cholinergic muscarinic antagonist scopolamine, the present experiments demonstrate, in a rat model, a critical role for the cortical muscarinic cholinergic system in feature binding. Specifically, ACh and the attentional resources that it supports are essential for the initial feature binding process but are not required to maintain neural representations of bound stimuli.

A Cross-Species Investigation of Acetylcholine, Attention, and Feature Binding:

The binding problem is the brains fundamental challenge to integrate sensory information to form a unified representation of a stimulus. A recent nonhuman animal model suggests that acetylcholine serves as the neuromodulatory substrate for feature binding. We hypothesized that this animal model of cholinergic contributions to feature binding may be an analogue of human attention. To test this hypothesis, we conducted a cross-species study in which rats and humans learned comparable intramodal feature-conjunction (FC) and feature-singleton (FS) tasks. We challenged the cholinergic system of rats using the muscarinic antagonist scopolamine (0.2 mg/kg) and challenged the attentional system of humans by dividing attention. The two manipulations yielded strikingly similar patterns of behavior, impairing FC acquisition, while sparing FS acquisition and FC retrieval. These cross-species findings support the hypothesis that cholinergically driven attentional processes are essential to feature binding at encoding, but are not required for retrieval of neural representations of bound stimuli.

Regional striatal volume abnormalities in schizophrenia: Effects of comorbidity for alcoholism, recency of alcoholic drinking, and antipsychotic medication type

Striatal structures form critical nodes of multiple circuits that are implicated in the pathophysiology of schizophrenia and alcoholism. Here, we examined the separate and combined effects of schizophrenia and alcoholism and effects of medication type and drinking recency on striatal volumes. Accordingly, we measured caudate nucleus, putamen, and nucleus accumbens in 27 schizophrenic, 25 alcohol-dependent, 19 comorbid (schizophrenia and alcohol dependence or abuse), and 51 age-matched control men. Schizophrenics were classified by antipsychotic medication (typical or atypical), and alcoholics were classified by recency of sobriety. All measured structures were smaller in the patient groups than the control group. The caudate deficit was comparable across groups, whereas putamen and nucleus accumbens deficits were greater in schizophrenia than alcoholism; comorbids fell between these groups. Schizophrenic patients treated with atypical medication showed greater volume deficits in the putamen than those treated with typical medication. Recently sober (<3 weeks) alcoholics had greater deficits in nucleus accumbens than longer sober drinkers. In conclusion, caudate, putamen, and nucleus accumbens exhibited different patterns of volume deficit in patients with alcoholism and schizophrenia alone, with no evidence for compounded deficits in comorbid patients. Further, these cross-sectional data provide indirect support for at least partial recovery of nucleus accumbens volume with sobriety in alcoholics, regardless of schizophrenia comorbidity.

Impaired Visual Search in Rats Reveals Cholinergic Contributions to Feature Binding in Visuospatial Attention

The visual search task established the feature integration theory of attention in humans and measures visuospatial attentional contributions to feature binding. We recently demonstrated that the neuromodulator acetylcholine (ACh), from the nucleus basalis magnocellularis (NBM), supports the attentional processes required for feature binding using a rat digging-based task. Additional research has demonstrated cholinergic contributions from the NBM to visuospatial attention in rats. Here, we combined these lines of evidence and employed visual search in rats to examine whether cortical cholinergic input supports visuospatial attention specifically for feature binding. We trained 18 male Long-Evans rats to perform visual search using touch screen-equipped operant chambers. Sessions comprised Feature Search (no feature binding required) and Conjunctive Search (feature binding required) trials using multiple stimulus set sizes. Following acquisition of visual search, 8 rats received bilateral NBM lesions using 192 IgG-saporin to selectively reduce cholinergic afferentation of the neocortex, which we hypothesized would selectively disrupt the visuospatial attentional processes needed for efficient conjunctive visual search. As expected, relative to sham-lesioned rats, ACh-NBM-lesioned rats took significantly longer to locate the target stimulus on Conjunctive Search, but not Feature Search trials, thus demonstrating that cholinergic contributions to visuospatial attention are important for feature binding in rats.

Learning to ignore: Acquisition of sustained attentional suppression

We examined whether the selection mechanisms committed to the suppression of ignored stimuli can be modified by experience to produce a sustained, rather than transient, change in behavior. Subjects repeatedly ignored the shape of stimuli, while attending to their color. On subsequent attention to shape, there was a robust and sustained decrement in performance that was selective to when shape was ignored across multiple-colortarget contexts, relative to a single-color-target context. Thus, amount of time ignored was not sufficient to induce a sustained performance decrement. Moreover, in this group, individual differences in initial color target selection were associated with the subsequent performance decrement when attending to previously ignored stimuli. Accompanying this sustained decrement in performance was a transfer in the locus of suppression from an exemplar (e.g., a circle) to a feature (i.e., shape) level of representation. These data suggest that learning can influence attentional selection by sustained attentional suppression of ignored stimuli.

Cholinergic Contributions to Supramodal Attentional Processes in Rats

Cholinergic neurotransmission has been shown to play an important role in modulating attentional processing of visual stimuli. However, it is not yet clear whether the neurochemical acetylcholine (ACh) is necessary exclusively for visual attention, or if it also contributes to attentional functions through some modality-independent (supramodal) mechanism. To answer this question, we examined the effects of reduced cortical cholinergic afferentation on both a traditional visual and a novel olfactory five-choice serial reaction time task (5-CSRTT), the benchmark rodent test of sustained attention in rats. Following the successful acquisition of both modalities of the task, the rats underwent either a cholinergic immunotoxic- or sham-lesion surgery of the nucleus basalis magnocellularis (NBM), the basal forebrain nuclei that provide the majority of neocortical ACh. Reduced cholinergic afferentation to the neocortex was induced by bilaterally infusing the cholinergic immunotoxin 192 IgG-saporin into the NBM. After surgery, ACh-NBM-lesioned rats performed comparably to sham-lesioned rats under the conditions of low attentional demand, but displayed behavioral decrements relative to the sham-lesioned rats when the attentional demands of the task were increased. Moreover, this decrement in attentional functioning correlated significantly with the number of choline acetyltransferase-immunoreactive cells in the NBM. Importantly, the nature of this behavioral decrement was identical in the visual and olfactory 5-CSRTTs. Together, these data suggest the presence of a supramodal attentional modulatory cortical network whose activity is dependent on cholinergic innervation from the NBM.

Distinguishing attentional gain and tuning in young and older adults

Here we examined with functional magnetic resonance imaging (fMRI) whether advanced age affects 2 mechanisms of attention that are widely thought to enhance signal processing in the sensory neocortex: gain and tuning. Healthy young and older adults discriminated faces under varying levels of object competition while fMRI was acquired. In young adults, cortical response magnitude to attended faces was maintained despite increasing competition, consistent with gain. Cortical response selectivity, indexed from repetition suppression, also increased only for attended faces despite increasing competition, consistent with tuning. Older adults exhibited intact gain, but altered tuning, with extrastriate cortical tuning determined by object salience rather than attention. Moreover, the magnitude of this susceptibility to stimulus-driven processing was associated with a redistribution of attention-driven competitive processes to the frontal cortices. These data indicate that although both gain and tuning are modulated by increased perceptual competition, they are functionally dissociable in the extrastriate cortices, exhibit differential susceptibility to advanced aging, and spare the frontal cortices a considerable processing burden through early selection.