The neural correlates of consciousness: An analysis of cognitive skill learning

This paper presents a functional brain-imaging strategy designed to isolate neural correlates of consciousness in humans. This strategy is based on skill learning. In the example presented (rapidly generating verbs for visually presented nouns), a cognitive skill is examined before and after practice. As shown, there are marked qualitative di¡erences in the neural circuitry supporting performance of this task in the naive and practised state that include, importantly, both increases and decreases from the baseline activity of the brain

Resting state functional connectivity in early blind humans

Task-based neuroimaging studies in early blind humans (EB) have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS). A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity

On the existence of a generalized non-specific task-dependent network

In this paper we suggest the existence of a generalized task-related cortical network that is up-regulated whenever the task to be performed requires the allocation of generalized non-specific cognitive resources, independent of the specifics of the task to be performed. We have labeled this general purpose network, the extrinsic mode network (EMN) as complementary to the default mode network (DMN), such that the EMN is down-regulated during periods of task-absence, when the DMN is up-regulated, and vice versa. We conceptualize the EMN as a cortical network for extrinsic neuronal activity, similar to the DMN as being a cortical network for intrinsic neuronal activity. The EMN has essentially a fronto-temporo-parietal spatial distribution, including the inferior and middle frontal gyri, inferior parietal lobule, supplementary motor area, inferior temporal gyrus. We hypothesize that this network is always active regardless of the cognitive task being performed. We further suggest that failure of network up- and down-regulation dynamics may provide neuronal underpinnings for cognitive impairments seen in many mental disorders, such as, e.g., schizophrenia. We start by describing a common observation in functional imaging, the close overlap in fronto-parietal activations in healthy individuals to tasks that denote very different cognitive processes. We now suggest that this is because the brain utilizes the EMN network as a generalized response to tasks that exceeds a cognitive demand threshold and/or requires the processing of novel information. We further discuss how the EMN is related to the DMN, and how a network for extrinsic activity is related to a network for intrinsic activity. Finally, we discuss whether the EMN and DMN networks interact in a common single brain system, rather than being two separate and independent brain systems

Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression

Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT). We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the ACC, but not the DLPFC, predict improvement in depression symptoms, and moreover, pretreatment ACC signaling predicts both depression severity and the likelihood of SNT treatment response. Taken together, our findings suggest that ACC-based directed signaling patterns in rs-fMRI are a potential biomarker of MDD

Functional Brain Imaging of Young, Nondemented, and Demented Older Adults

Brain imaging based on functional MRI (fMRI) provides a powerful tool for characterizing age-related changes in functional anatomy. However, between-population comparisons confront potential differences in measurement properties. The present experiment explores the feasibility of conducting fMRI studies in nondemented and demented older adults by measuring hemodynamic response properties in an event-related design. A paradigm involving repeated presentation of sensory-motor response trials was administered to 41 participants (14 young adults, 14 nondemented older adults, and 13 demented older adults). For half of the trials a single sensory-motor event was presented in isolation and in the other half in pairs. Hemodynamic response characteristics to the isolated events allowed basic response properties (e.g., amplitude and variance) between subject groups to be contrasted. The paired events further allowed the summation properties of the hemodynamic response to be characterized. Robust and qualitatively similar activation maps were produced for all subject groups. Quantitative results showed that for certain regions, such as in the visual cortex, there were marked reductions in the amplitude of the hemodynamic response in older adults. In other regions, such as in the motor cortex, relatively intact response characteristics were observed. These results suggest caution should be exhibited in interpreting simple main effects in response amplitude between subject groups. However, across all regions examined, the summation of the hemodynamic response over trials was highly similar between groups. This latter finding suggests that, even if absolute measurement differences do exist between subject groups, relative activation change should be preserved. Designs that rely on group interactions between task conditions, parametric manipulations, or group interactions between regions should provide valuable data for making inferences about functional-anatomic changes between different populations.Psycholog

Loss of intranetwork and internetwork resting state functional connections with Alzheimer\u27s disease progression

Alzheimer\u27s disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain\u27s functional organization

On the role of the corpus callosum in interhemispheric functional connectivity in humans

Resting state functional connectivity is defined in terms of temporal correlations between physiologic signals, most commonly studied using functional magnetic resonance imaging. Major features of functional connectivity correspond to structural (axonal) connectivity. However, this relation is not one-to-one. Interhemispheric functional connectivity in relation to the corpus callosum presents a case in point. Specifically, several reports have documented nearly intact interhemispheric functional connectivity in individuals in whom the corpus callosum (the major commissure between the hemispheres) never develops. To investigate this question, we assessed functional connectivity before and after surgical section of the corpus callosum in 22 patients with medically refractory epilepsy. Section of the corpus callosum markedly reduced interhemispheric functional connectivity. This effect was more profound in multimodal associative areas in the frontal and parietal lobe than primary regions of sensorimotor and visual function. Moreover, no evidence of recovery was observed in a limited sample in which multiyear, longitudinal follow-up was obtained. Comparison of partial vs. complete callosotomy revealed several effects implying the existence of polysynaptic functional connectivity between remote brain regions. Thus, our results demonstrate that callosal as well as extracallosal anatomical connections play a role in the maintenance of interhemispheric functional connectivity

Retinotopic organization of human visual cortex mapped with positron-emission tomography

The retinotopic organization of primary visual cortex was mapped in normal human volunteers. Positron-emission tomographic measurements of regional cerebral blood flow were employed to detect focal functional brain activation. Oxygen-15-labeled water, delivered by intravenous bolus, was used as the blood flow tracer to allow multiple stimulated- state (n = 5) and control-state (n = 3) measurements to be acquired for each of 7 subjects. Responses were identified by applying a maximum- detection algorithm to subtraction-format images of the stimulus- induced change in cerebral blood flow. Response locales were described using a standardized system of stereotactic coordinates. Changes in stimulus location (macular, perimacular, peripheral, upper-field, lower- field) caused systematic, highly significant changes in response locale within visual cortex. Discrete extrastriate visual responses were also observed