Author: bgross

Propofol Sedation Alters Perceptual and Cognitive Functions in Healthy Volunteers as Revealed by Functional Magnetic Resonance Imaging

https://anesthesiology.pubs.asahq.org/article.aspx?articleid=2730436

William L. Gross, Kathryn K. Lauer, Xiaolin Liu, Christopher J. Roberts, Suyan Liu, Suneeta Gollapudy, Jeffrey R. Binder, Shi-Jiang Li, Anthony G. Hudetz; Propofol Sedation Alters Perceptual and Cognitive Functions in Healthy Volunteers as Revealed by Functional Magnetic Resonance Imaging. Anesthesiology 2019;. doi: 10.1097/ALN.0000000000002669.

Background: Elucidating networks underlying conscious perception is important to understanding the mechanisms of anesthesia and consciousness. Previous studies have observed changes associated with loss of consciousness primarily using resting paradigms. The authors focused on the effects of sedation on specific cognitive systems using task-based functional magnetic resonance imaging. The authors hypothesized deepening sedation would degrade semantic more than perceptual discrimination.

Methods: Discrimination of pure tones and familiar names were studied in 13 volunteers during wakefulness and propofol sedation targeted to light and deep sedation. Contrasts highlighted specific cognitive systems: auditory/motor (tones vs. fixation), phonology (unfamiliar names vs. tones), and semantics (familiar vs. unfamiliar names), and were performed across sedation conditions, followed by region of interest analysis on representative regions.

Results: During light sedation, the spatial extent of auditory/motor activation was similar, becoming restricted to the superior temporal gyrus during deep sedation. Region of interest analysis revealed significant activation in the superior temporal gyrus during light (t[17] = 9.71, P < 0.001) and deep sedation (t[19] = 3.73, P = 0.001). Spatial extent of the phonologic contrast decreased progressively with sedation, with significant activation in the inferior frontal gyrus maintained during light sedation (t [35] = 5.17, P < 0.001), which didn’t meet criteria for significance in deep sedation (t[38] = 2.57, P = 0.014). The semantic contrast showed a similar pattern, with activation in the angular gyrus during light sedation (t[16] = 4.76, P = 0.002), which disappeared in deep sedation (t [18] = 0.35, P = 0.731).

Conclusions: Results illustrate broad impairment in cognitive cortex during sedation, with activation in primary sensory cortex beyond loss of consciousness. These results agree with clinical experience: a dose-dependent reduction of higher cognitive functions during light sedation, despite partial preservation of sensory processes through deep sedation.

Lesion localization of speech comprehension deficits in chronic aphasia

Objective: Voxel-based lesion-symptom mapping (VLSM) was used to localize impairments specific to multiword (phrase and sentence) spoken language comprehension.

Methods: Participants were 51 right-handed patients with chronic left hemisphere stroke. They performed an auditory description naming (ADN) task requiring comprehension of a verbal description, an auditory sentence comprehension (ASC) task, and a picture naming (PN) task. Lesions were mapped using high-resolution MRI. VLSM analyses identified the lesion correlates of ADN and ASC impairment, first with no control measures, then adding PN impairment as a covariate to control for cognitive and language processes not specific to spoken language.

Results: ADN and ASC deficits were associated with lesions in a distributed frontal-temporal parietal language network. When PN impairment was included as a covariate, both ADN and ASC deficits were specifically correlated with damage localized to the mid-to-posterior portion of the middle temporal gyrus (MTG).

Conclusions: Damage to the mid-to-posterior MTG is associated with an inability to integrate multiword utterances during comprehension of spoken language. Impairment of this integration process likely underlies the speech comprehension deficits characteristic of Wernicke aphasia.

Pillay SB, Binder JR, Humphries CJ, Gross WL, Book, DS (2017) Lesion localization of speech comprehension deficits in chronic aphasia. Neurology; doi: 10.1212/WNL.0000000000003683

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Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness

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Recent studies indicate that spontaneous low-frequency fluctuations (LFFs) of resting-state functional magnetic resonance imaging (rs-fMRI) blood oxygen level-dependent (BOLD) signals are driven by the slow (<0.1 Hz) modulation of ongoing neuronal activity synchronized locally and across remote brain regions. How regional LFFs of the BOLD fMRI signal are altered during anesthetic-induced alteration of consciousness is not well understood. Using rs-fMRI in 15 healthy participants, we show that during administration of propofol to achieve loss of behavioral responsiveness indexing unconsciousness, the fractional amplitude of LFF (fALFF index) was reduced in comparison to wakeful baseline in the anterior frontal regions, temporal pole, hippocampus, parahippocampal gyrus, and amygdala. Such changes were absent in large areas of the motor, parietal, and sensory cortices. During light sedation characterized by the preservation of overt responsiveness and therefore consciousness, fALFF was reduced in the subcortical areas, temporal pole, medial orbital frontal cortex, cingulate cortex, and cerebellum. Between light sedation and deep sedation, fALFF was reduced primarily in the medial and dorsolateral frontal areas. The preferential reduction of LFFs in the anterior frontal regions is consistent with frontal to sensory-motor cortical disconnection and may contribute to the suppression of consciousness during general anesthesia.

Liu, X, Lauer, KK, Ward, BD, Roberts, C, Liu, S, Gollapudy, S, Rohloff, R, Gross, WL, Chen, G, Xu, Z, Binder, JR, Li, SJ, Hudetz, AG (2016) Propofol attenuates low-frequency fluctuations of resting-state fMRI BOLD signal in the anterior frontal cortex upon loss of consciousness. Neuroimage; doi:10.1016/j.neuroimage.2016.12.043

High-resolution parcellation of brain connectivity improves differentiation of states of consciousness during graded propofol sedation

Liu, X, Lauer, KK, Ward, BD, Roberts, C, Liu, S, Gollapudy, S, Rohloff, R, Gross, WL, Chen, G, Binder, JR, Li, SJ, Hudetz, AJ (2016) High-resolution parcellation of brain connectivity improves differentiation of states of consciousness during graded propofol sedation. Brain Connectivity. In review

Surface errors without semantic impairment in acquired dyslexia: a voxel-based lesion–symptom mapping study

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Patients with surface dyslexia have disproportionate difficulty pronouncing irregularly spelled words (e.g. pint), suggesting im- paired use of lexical-semantic information to mediate phonological retrieval. Patients with this deficit also make characteristic ‘regularization’ errors, in which an irregularly spelled word is mispronounced by incorrect application of regular spelling-sound correspondences (e.g. reading plaid as ‘played’), indicating over-reliance on sublexical grapheme–phoneme correspondences. We examined the neuroanatomical correlates of this specific error type in 45 patients with left hemisphere chronic stroke. Voxel-based lesion–symptom mapping showed a strong positive relationship between the rate of regularization errors and damage to the posterior half of the left middle temporal gyrus. Semantic deficits on tests of single-word comprehension were generally mild, and these deficits were not correlated with the rate of regularization errors. Furthermore, the deep occipital-temporal white matter locus associated with these mild semantic deficits was distinct from the lesion site associated with regularization errors. Thus, in contrast to patients with surface dyslexia and semantic impairment from anterior temporal lobe degeneration, surface errors in our patients were not related to a semantic deficit. We propose that these patients have an inability to link intact semantic represen- tations with phonological representations. The data provide novel evidence for a post-semantic mechanism mediating the produc- tion of surface errors, and suggest that the posterior middle temporal gyrus may compute an intermediate representation linking semantics with phonology.

Binder, JR, Pillay, SB, Humphries, CJ, Gross, WL, Graves, WW, Book, DS (2016) Surface errors without semantic impairment in acquired dyslexia: a voxel-based lesion–symptom mapping study. Brain; doi:10.1093/brain/aww029