Psychosis in the Context of Sodium Oxybate Therapy


Sodium oxybate (brand name Xyrem) is a sodium salt of gam- ma-hydroxybutyric acid (GHB), an endogenous CNS depres- sant, which is an effective treatment of narcolepsy. As a drug of abuse, GHB produces severe psychiatric side effects and with- drawal. However, there are no reports of these effects when us- ing 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 medi- cation, as well as withdrawal symptoms, even at clinical doses. Keywords: Sodium oxybate, narcolepsy, psychoses – substance- induced, substance withdrawal syndrome

Langford, J., & Gross, W. L. (2011). Psychosis in the context of sodium oxybate therapy. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 7(6), 665–666. doi:10.5664/jcsm.1478

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 N 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.

Binder JR, Gross WL, Allendorfer JB, Bonilha L, Chapin J, Edwards JC, Grabowski TJ, Langfitt JT, Loring DW, Lowe MJ, Koenig K, Morgan PS, Ojemann JG, Rorden C, Szaflarski JP, Tivarus ME, Weaver KE. (2011). Mapping anterior temporal lobe language areas with fMRI: a multicenter normative study. Neuroimage, 15;54(2), 1465-1475.

PhD dissertation: Using fMRI to Improve Outcome in the Surgical Treatment of Temporal Lobe Epilepsy


Temporal lobe epilepsy is a neurological disease that affects millions worldwide, and can be effectively treated through surgical resection of portions of the anterior temporal lobe (ATL). Though effective for seizure control, this surgery occasionally produces language and verbal memory deficits. The goal of this work was to improve language-mapping techniques using fMRI in order to better inform the surgeon prior to ATL resection.

This was approached in three main experiments. First, an ATL deactivation task was developed. Since the ATL is hypothesized to be involved in semantic memory processing, mathematical stimuli were used, which are strongly attentionally engaging, but do not contain much semantic content. This was compared to previously used tasks and shown to be superior at producing ATL deactivation.

Second, an activation task was designed using story passages, differing from many previous studies that have used single word stimuli to activate the ATL. This task was combined with the math baseline task to produce maximal contrast in the ATL.

Finally, an improved thresholding method is proposed that increases the consistency of fMRI maps in individual patients, adapted for the requirements of surgical planning. While traditional methods of thresholding are effective for research questions, use of activation maps for surgical planning requires an approach that is less sensitive to individual variability in noise level. This new method was shown to be superior to current methods at predicting patient outcome.

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, neuro- physiology 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 acti- vation 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 hippo- campi, posterior cingulate, and middle temporal gyri. Findings are discussed within the framework of recent proposals concerning the neural network of person identification.

Nielson KA, Seidenberg M, Woodard JL, Durgerian S, Zhang Q, Gross WL, Gander A, Guidotti LM, Antuono P, Rao SM (2010). Common neural systems associated with the recognition of famous faces and names: an event-related fMRI study. Brain Cogn. 72(3), 491-498.

Hippocampal differentiation without recognition: An fMRI analysis of the contextual cueing task


A central role of the hippocampus is to consolidate conscious forms of learning and memory, while performance on implicit tasks appears to depend upon other structures. Recently, considerable debate has emerged about whether hippocampal-dependent tasks necessarily entail task awareness. In the contextual cueing task, repetition facilitation is implicit, but impaired in patients with amnesia. Whether the hippocampus alone or other MTL structures are required is unclear. Event-related functional magnetic resonance imaging revealed hippocampal activity that differentiates novel from repeated arrays. This pattern of results was observed without recognition of the repeating arrays. This finding provides support for the claim that the hippocampus is involved in processes outside the domain of conscious learning and memory.

Greene AJ, Gross WL, Elsinger CL, Rao SM (2007). Hippocampal differentiation without recognition: An fMRI analysis of the contextual cueing task. Learn Mem, 14(8), 548-553.

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 res- onance 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; sev- eral 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 disso- ciated 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, ac- quiring these ‘‘inner pairs’’ corresponded to greater hippo- campal activation than the ‘‘outer pairs’’ (A > B, D > E) for all participants. However, a distinct pattern of hippocampal ac- tivity 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 be- cause the premise pair acquisition necessary for inference is hippocampal-dependent; (4) We found B > D related hippo- campal activity at test that is anatomically consistent with pre- consolidation recall effects shown in other studies.

Greene AJ, Gross WL, Elsinger CL, Rao SM (2006). An FMRI analysis of the human hippocampus: inference, context, and task awareness. J Cogn Neurosci, 18(7), 1156-1173.