Josef Parvizi

Subcortical and cortical brain activity during the feeling of self-generated emotions

In a series of [15O]PET experiments aimed at investigating the neural basis of emotion and feeling, 41 normal subjects recalled and re-experienced personal life episodes marked by sadness, happiness, anger or fear. We tested the hypothesis that the process of feeling emotions requires the participation of brain regions, such as the somatosensory cortices and the upper brainstem nuclei, that are involved in the mapping and/or regulation of internal organism states. Such areas were indeed engaged, underscoring the close relationship between emotion and homeostasis. The findings also lend support to the idea that the subjective process of feeling emotions is partly grounded in dynamic neural maps, which represent several aspects of the organisms continuously changing internal state.

Consciousness and the brainstem

In the first part of this article we summarize a theoretical framework and a set of hypotheses aimed at accounting for consciousness in neurobiological terms. The basic form of consciousness, core consciousness is placed in the context of life regulation; it is seen as yet another level of biological processing aimed at ensuring the homeostatic balance of a living organism; and the representation of the current organism state within somato-sensing structures is seen as critical to its development. Core consciousness is conceived as the imaged relationship of the interaction between an object and the changed organism state it causes. In the second part of the article we discuss the functional neuroanatomy of nuclei in the brainstem reticular formation because they constitute the basic set of somato-sensing structures necessary for core consciousness and its core self to emerge. The close relationship between the mechanisms underlying cortical activation and the bioregulatory mechanisms outlined here is entirely compatible with the classical idea that the reticular formation modulates the electrophysiological activity of the cerebral cortex. However, in the perspective presented here, that modulation is placed in the setting of the organisms homeostatic regulation.

Neural connections of the posteromedial cortex in the macaque

The posterior cingulate and the medial parietal cortices constitute an ensemble known as the posteromedial cortex (PMC), which consists of Brodmann areas 23, 29, 30, 31, and 7m. To understand the neural relationship of the PMC with the rest of the brain, we injected its component areas with four different anterograde and retrograde tracers in the cynomolgus monkey and found that all PMC areas are interconnected with each other and with the anterior cingulate, the mid-dorsolateral prefrontal, the lateral parietal cortices, and area TPO, as well as the thalamus, where projections from some of the PMC areas traverse in an uninterrupted bar-like manner, the dorsum of this structure from the posteriormost nuclei to its rostralmost tip. All PMC regions also receive projections from the claustrum and the basal forebrain and project to the caudate, the basis pontis, and the zona incerta. Moreover, the posterior cingulate areas are interconnected with the parahippocampal regions, whereas the medial parietal cortex projects only sparsely to the presubiculum. Although local interconnections and shared remote connections of all PMC components suggest a functional relationship among them, the distinct connections of each area with different neural structures suggests that distinct functional modules may be operating within the PMC. Our study provides a large-scale map of the PMC connections with the rest of the brain, which may serve as a useful tool for future studies of this cortical region and may contribute to elucidating its intriguing pattern of activity seen in recent functional imaging studies.

Shifts in Gamma Phase–Amplitude Coupling Frequency from Theta to Alpha Over Posterior Cortex During Visual Tasks

The phase of ongoing theta (4–8 Hz) and alpha (8–12 Hz) electrophysiological oscillations is coupled to high gamma (80–150 Hz) amplitude, which suggests that low-frequency oscillations modulate local cortical activity. While this phase–amplitude coupling (PAC) has been demonstrated in a variety of tasks and cortical regions, it has not been shown whether task demands differentially affect the regional distribution of the preferred low-frequency coupling to high gamma. To address this issue we investigated multiple-rhythm theta/alpha to high gamma PAC in two subjects with implanted subdural electrocorticographic grids. We show that high gamma amplitude couples to the theta and alpha troughs and demonstrate that, during visual tasks, alpha/high gamma coupling preferentially increases in visual cortical regions. These results suggest that low-frequency phase to high-frequency amplitude coupling is modulated by behavioral task and may reflect a mechanism for selection between communicating neuronal networks.

Electrical Stimulation of Human Fusiform Face-Selective Regions Distorts Face Perception

Face-selective neural responses in the human fusiform gyrus have been widely examined. However, their causal role in human face perception is largely unknown. Here, we used a multimodal approach of electrocorticography (ECoG), high-resolution functional magnetic resonance imaging (fMRI), and electrical brain stimulation (EBS) to directly investigate the causal role of face-selective neural responses of the fusiform gyrus (FG) in face perception in a patient implanted with subdural electrodes in the right inferior temporal lobe. High-resolution fMRI identified two distinct FG face-selective regions [mFus-faces and pFus-faces (mid and posterior fusiform, respectively)]. ECoG revealed a striking anatomical and functional correspondence with fMRI data where a pair of face-selective electrodes, positioned 1 cm apart, overlapped mFus-faces and pFus-faces, respectively. Moreover, electrical charge delivered to this pair of electrodes induced a profound face-specific perceptual distortion during viewing of real faces. Specifically, the subject reported a “metamorphosed” appearance of faces of people in the room. Several controls illustrate the specificity of the effect to the perception of faces. EBS of mFus-faces and pFus-faces neither produced a significant deficit in naming pictures of famous faces on the computer, nor did it affect the appearance of nonface objects. Further, the appearance of faces remained unaffected during both sham stimulation and stimulation of a pair of nearby electrodes that were not face-selective. Overall, our findings reveal a striking convergence of fMRI, ECoG, and EBS, which together offer a rare causal link between functional subsets of the human FG network and face perception.

The selective vulnerability of brainstem nuclei to Alzheimer's disease

In a study of thioflavin S–stained serial sections from the entire brainstem, we found that the inferior and superior colliculi and the autonomic, monoaminergic, cholinergic, and classical reticular nuclei were affected with varying degrees of severity and frequencies in 32 patients with Alzheimers disease, whereas no changes were seen in the brainstems of 26 control subjects. The majority of the affected nuclei in patients with Alzheimers disease exhibit either neurofibrillary tangles or senile plaques, and only a few display both. However, when sections were immunostained with the antibodies 10D5 and AT8 or ALZ50, both β‐amyloid and hyperphosphorylated epitopes of tau protein were found to be present in various concentrations in all the affected nuclei. Our findings suggest that each brainstem nucleus has a distinct vulnerability to Alzheimers disease–related pathological changes. Given that each nucleus has idiosyncratic neuroanatomical connections and prevailing neurochemical characteristics, the heterogeneous collection of brainstem nuclei can be considered a suitable anatomical ground for further investigation of selective vulnerability in Alzheimers disease. The finding of severe pathological changes in some brainstem nuclei also raises the possibility that the dysfunction of these nuclei may contribute to the cognitive defects and increased rates of morbidity and mortality in patients with Alzheimers disease. Ann Neurol 2001;49:53–66

Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging

Here, we describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent quantitative estimate of MTV can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second, we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition.

A Brain Area for Visual Numerals

Is there a distinct area within the human visual system that has a preferential response to numerals, as there is for faces, words, or scenes? We addressed this question using intracranial electrophysiological recordings and observed a significantly higher response in the high-frequency broadband range (high γ, 65–150 Hz) to visually presented numerals, compared with morphologically similar (i.e., letters and false fonts) or semantically and phonologically similar stimuli (i.e., number words and non-number words). Anatomically, this preferential response was consistently localized in the inferior temporal gyrus and anterior to the temporo-occipital incisure. This region lies within or close to the fMRI signal-dropout zone produced by the nearby auditory canal and venous sinus artifacts, an observation that may account for negative findings in previous fMRI studies of preferential response to numerals. Because visual numerals are culturally dependent symbols that are only learned through education, our novel finding of anatomically localized preferential response to such symbols provides a new example of acquired category-specific responses in the human visual system.

Electrical stimulation of the human brain: perceptual and behavioral phenomena reported in the old and new literature

In this review, we summarize the subjective experiential phenomena and behavioral changes that are caused by electrical stimulation of the cerebral cortex or subcortical nuclei in awake and conscious human subjects. Our comprehensive review contains a detailed summary of the data obtained from electrical brain stimulation (EBS) in humans in the last 100 years. Findings from the EBS studies may provide an additional layer of information about the neural correlates of cognition and behavior in healthy human subjects, or the neuroanatomy of illusions and hallucinations in patients with psychosis and the brain symptomatogenic zones in patients with epilepsy. We discuss some fundamental concepts, issues, and remaining questions that have defined the field of EBS, and review the current state of knowledge about the mechanism of action of EBS suggesting that the modulation of activity within a localized, but distributed, neuroanatomical network might explain the perceptual and behavioral phenomena that are reported during focal electrical stimulation of the human brain.

Differential electrophysiological response during rest, self-referential, and non–self-referential tasks in human posteromedial cortex

The electrophysiological basis for higher brain activity during rest and internally directed cognition within the human default mode network (DMN) remains largely unknown. Here we use intracranial recordings in the human posteromedial cortex (PMC), a core node within the DMN, during conditions of cued rest, autobiographical judgments, and arithmetic processing. We found a heterogeneous profile of PMC responses in functional, spatial, and temporal domains. Although the majority of PMC sites showed increased broad gamma band activity (30–180 Hz) during rest, some PMC sites, proximal to the retrosplenial cortex, responded selectively to autobiographical stimuli. However, no site responded to both conditions, even though they were located within the boundaries of the DMN identified with resting-state functional imaging and similarly deactivated during arithmetic processing. These findings, which provide electrophysiological evidence for heterogeneity within the core of the DMN, will have important implications for neuroimaging studies of the DMN.