William L. Gross

Mapping anterior temporal lobe language areas with fMRI: A multicenter normative study

Removal of the anterior temporal lobe (ATL) is an effective surgical treatment for intractable temporal lobe epilepsy but carries a risk of language and verbal memory deficits. Preoperative localization of functional zones in the ATL might help reduce these risks, yet fMRI protocols in current widespread use produce very little activation in this region. Based on recent evidence suggesting a role for the ATL in semantic integration, we designed an fMRI protocol comparing comprehension of brief narratives (Story task) with a semantically shallow control task involving serial arithmetic (Math task). The Story > Math contrast elicited strong activation throughout the ATL, lateral temporal lobe, and medial temporal lobe bilaterally in an initial cohort of 18 healthy participants. The task protocol was then implemented at 6 other imaging centers using identical methods. Data from a second cohort of participants scanned at these centers closely replicated the results from the initial cohort. The Story-Math protocol provides a reliable method for activation of surgical regions of interest in the ATL. The bilateral activation supports previous claims that conceptual processing involves both temporal lobes. Used in combination with language lateralization measures, reliable ATL activation maps may be useful for predicting cognitive outcome in ATL surgery, though the validity of this approach needs to be established in a prospective surgical series.

An fMRI Analysis of the Human Hippocampus: Inference, Context, and Task Awareness

The hippocampus is critical for encoding and retrieving semantic and episodic memories. Animal studies indicate that the hippocampus is also required for relational learning tasks. A prototypical relational learning task, and the one investigated in this experiment, using event-related functional magnetic resonance imaging, is the transitive inference (TI) task. In the TI task, participants were to choose between A and B (A?B) and learned by trial and error to choose A (A > B). There were four such premise pairs during a training (A > B, B > C, C > D, D > E). These can be acquired distinctly or can be organized into a superordinate hierarchy (A > B > C > D > E), which would efficiently represent all the learned relations and allow inferences (e.g., B > D). At test there was no reinforcement: In addition to premise pairs, untrained pairings were introduced (e.g., A?E, B?D). Correctly inferring that B > D is taken as evidence for the formation of a superordinate hierarchy; several alternatives to the superordinate hierarchy hypothesis are considered. Awareness of the formation of this hierarchy was measured by a postscan questionnaire. Four main findings are reported: (1) Inferential performance and task awareness dissociated behaviorally and at the level of hemodynamic response; (2) As expected, performance on the inferred relation, B > D, corresponded to the ability to simultaneously acquire B > C and C > D premise pairs during training; (3) Interestingly, acquiring these inner pairs corresponded to greater hippocampal activation than the outer pairs (A > B, D > E) for all participants. However, a distinct pattern of hippocampal activity for these inner pairs differentiated those able to perform the inferential discrimination, B > D, at test. Because these inner premise pairs require contextual discrimination (e.g., C is incorrect in the context of B but correct in the context of D), we argue that the TI task is hippocampal-dependent because the premise pair acquisition necessary for inference is hippocampal-dependent; (4) We found B > D related hippocampal activity at test that is anatomically consistent with preconsolidation recall effects shown in other studies.

Common Neural Systems Associated with the Recognition of Famous Faces and Names: An Event-Related fMRI Study.

Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related functional-MRI in 17 healthy participants to directly compare activation in response to randomly presented famous and non-famous names and faces (25 stimuli in each of the four categories). Findings indicated distinct areas of activation that differed for faces and names in regions typically associated with pre-semantic perceptual processes. In contrast, overlapping brain regions were activated in areas associated with the retrieval of biographical knowledge and associated social affective features. Specifically, activation for famous faces was primarily right lateralized and famous names were left-lateralized. However, for both stimuli, similar areas of bilateral activity were observed in the early phases of perceptual processing. Activation for fame, irrespective of stimulus modality, activated an extensive left hemisphere network, with bilateral activity observed in the hippocampi, posterior cingulate, and middle temporal gyri. Findings are discussed within the framework of recent proposals concerning the neural network of person identification.

Analogical inference: the role of awareness in abstract learning.

The acquisition and flexible expression of complex relations is often attributed to declarative memory processes. The extent to which such tasks may be done implicitly has not been sufficiently explored. We report that analogical or transfer processes may be accomplished implicitly. Our analogy task requires acquisition of a transverse patterning set, and then tests for transfer on an unrelated set. Participants learn the relations A>B (given a choice between A and B choose A) and B>C and the unrelated set X>Y and Y>Z. Only the experimental group was trained on the transverse pair C>A. At test all trials are unreinforced: A?B, B?C, A?C, X?Y, Y?Z, X?Z. Analogy was observed when the experimental group chose Z>X at greater frequency than controls who uniformly chose X>Z. Analogy occurred with or without awareness of the transfer. The capacity to transfer relations to an analogous set demonstrates a level of flexibility and abstraction not generally thought to be possible for implicit processes.

Predicting brain activation patterns associated with individual lexical concepts based on five sensory-motor attributes

While major advances have been made in uncovering the neural processes underlying perceptual representations, our grasp of how the brain gives rise to conceptual knowledge remains relatively poor. Recent work has provided strong evidence that concepts rely, at least in part, on the same sensory and motor neural systems through which they were acquired, but it is still unclear whether the neural code for concept representation uses information about sensory-motor features to discriminate between concepts. In the present study, we investigate this question by asking whether an encoding model based on five semantic attributes directly related to sensory-motor experience - sound, color, visual motion, shape, and manipulation - can successfully predict patterns of brain activation elicited by individual lexical concepts. We collected ratings on the relevance of these five attributes to the meaning of 820 words, and used these ratings as predictors in a multiple regression model of the fMRI signal associated with the words in a separate group of participants. The five resulting activation maps were then combined by linear summation to predict the distributed activation pattern elicited by a novel set of 80 test words. The encoding model predicted the activation patterns elicited by the test words significantly better than chance. As expected, prediction was successful for concrete but not for abstract concepts. Comparisons between encoding models based on different combinations of attributes indicate that all five attributes contribute to the representation of concrete concepts. Consistent with embodied theories of semantics, these results show, for the first time, that the distributed activation pattern associated with a concept combines information about different sensory-motor attributes according to their respective relevance. Future research should investigate how additional features of phenomenal experience contribute to the neural representation of conceptual knowledge.

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.

Psychosis in the Context of Sodium Oxybate Therapy

Sodium oxybate (brand name Xyrem) is a sodium salt of gamma-hydroxybutyric acid (GHB), an endogenous CNS depressant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and withdrawal. However, there are no reports of these effects when using clinically recommended doses. This paper presents a case of a patient who developed altered mental status while taking the recommended dose of sodium oxybate and subsequently became psychotic upon abrupt discontinuation of the medication. It is important for prescribers of sodium oxybate to be aware of the possibility of significant psychiatric side effects of this medication, as well as withdrawal symptoms, even at clinical doses.

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

ABSTRACT 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.

Alternative thresholding methods for fMRI data optimized for surgical planning.

Current methods for thresholding functional magnetic resonance imaging (fMRI) maps are based on the well-known hypothesis-test framework, optimal for addressing novel theoretical claims. However, these methods as typically practiced have a strong bias toward protecting the null hypothesis, and thus may not provide an optimal balance between specificity and sensitivity in forming activation maps for surgical planning. Maps based on hypothesis-test thresholds are also highly sensitive to sample size and signal-to-noise ratio, whereas many clinical applications require methods that are robust to these effects. We propose a new thresholding method, optimized for surgical planning, based on normalized amplitude thresholding. We show that this method produces activation maps that are more reproducible and more predictive of postoperative cognitive outcome than maps produced with current standard thresholding methods.

Fine-Grained Parcellation of Brain Connectivity Improves Differentiation of States of Consciousness During Graded Propofol Sedation

Conscious perception relies on interactions between spatially and functionally distinct modules of the brain at various spatiotemporal scales. These interactions are altered by anesthesia, an intervention that leads to fading consciousness. Relatively little is known about brain functional connectivity and its anesthetic modulation at a fine spatial scale. Here, we used functional imaging to examine propofol-induced changes in functional connectivity in brain networks defined at a fine-grained parcellation based on a combination of anatomical and functional features. Fifteen healthy volunteers underwent resting-state functional imaging in wakeful baseline, mild sedation, deep sedation, and recovery of consciousness. Compared with wakeful baseline, propofol produced widespread, dose-dependent functional connectivity changes that scaled with the extent to which consciousness was altered. The dominant changes in connectivity were associated with the frontal lobes. By examining node pairs that demonstrated a trend of functional connectivity change between wakefulness and deep sedation, quadratic discriminant analysis differentiated the states of consciousness in individual participants more accurately at a fine-grained parcellation (e.g., 2000 nodes) than at a coarse-grained parcellation (e.g., 116 anatomical nodes). Our study suggests that defining brain networks at a high granularity may provide a superior imaging-based distinction of the graded effect of anesthesia on consciousness.