Remote Effects of Hippocampal Sclerosis on Effective Connectivity during Working Memory Encoding: A Case of Connectional Diaschisis?

Abstract

Accumulating evidence suggests a role for the medial temporal lobe (MTL) in working memory (WM). However, little is known concerning its functional interactions with other cortical regions in the distributed neural network subserving WM. To reveal these, we availed of subjects with MTL damage and characterized changes in effective connectivity while subjects engaged in WM task. Specifically, we compared dynamic causal models, extracted from magnetoencephalographic recordings during verbal WM encoding, in temporal lobe epilepsy patients (with left hippocampal sclerosis) and controls. Bayesian model comparison indicated that the best model (across subjects) evidenced bilateral, forward, and backward connections, coupling inferior temporal cortex (ITC), inferior frontal cortex (IFC), and MTL. MTL damage weakened backward connections from left MTL to left ITC, a decrease accompanied by strengthening of (bidirectional) connections between IFC and MTL in the contralesional hemisphere. These findings provide novel evidence concerning functional interactions between nodes of this fundamental cognitive network and sheds light on how these interactions are modified as a result of focal damage to MTL. The findings highlight that a reduced (top-down) influence of the MTL on ipsilateral language regions is accompanied by enhanced reciprocal coupling in the undamaged hemisphere providing a first demonstration of “connectional diaschisis.”

Visual object naming in patients with small lesions centered at the left temporopolar region

“…Of interest, this pattern took place in a context of mild semantic dysfunction that was evident in different types and modalities of semantic tasks, thus supporting the critical role of the left temporal pole for conceptual knowledge (Bruffaerts et al 2013;Clarke et al 2011Clarke et al , 2013Chan et al 2011;Mesulam et al 2013;Peelen and Caramazza 2012). It is important to highlight that, although current results demonstrate that unilateral damage to the left temporal pole can produce a significant semantic impairment, it is, however, far from the devastating degradation observed in semantic dementia and other bilateral conditions (Antonucci et al 2008;Lambon Ralph et al 2010a, 2012Lambon Ralph et al 2012;Schapiro et al 2013;Tsapkini et al 2011). PC was supported by a Ramon y Cajal Fellowship from the Spanish Ministry of Science and Innovation (RYC-2010-05748). CP was supported by Spanish Ministry of Science and Education (AP2009-4131).…”

“…This is not to say that the temporal pole is the only region involved (Binney et al 2012b). Instead, impaired performance may not be caused solely by local dysfunction of the damaged ATL, or by the disruption that the epileptogenic activity can cause in other brain areas, but by the local and remote changes in the interactions among regions that constitute the network (Campo et al 2012;Carrera and Tononi 2014). Specifically, alteration of the structural and/or functional connectivity from the temporal pole to a speech production mechanism via uncinate fasciculus (Acosta-Cabronero et al 2011;Agosta et al 2010;Blaizot et al 2010;Dick and Tremblay 2012;Han et al 2013;Lambon Ralph 2014;Pascual et al 2014), and from posterior temporal regions via inferior longitudinal fasciculus (Behrmann and Plaut 2013;Campo et al 2013;Clarke et al 2011;Fan et al 2014;Guo et al 2013) could be the mechanism underlying the observed pattern of impairment.…”

“…We also analyzed the proportion of error types. Semantic error production was classified as one of the following subtypes: pure semantic errors-''substituted nouns that related to the target either taxonomically or associatively, and that were not also phonologically related''; and omissions including no response or partial description without providing a name (Lambon Ralph et al 2010a, 2012. Each type of error was divided by the total amount of trials (Schwartz et al 2009).…”

“…Finally, one question that ''still needs to be answered is whether unilateral temporal pole damage alone'' can cause damage to object naming (Tsapkini et al 2011). The few studies that have addressed this issue have evaluated naming abilities in patients with unilateral lesions that were extended over large brain areas covering different subregions, mainly stroke and temporal lobe surgical resection (Antonucci et al 2008;Lambon Ralph et al 2010a, 2012Tsapkini et al 2011). To better understand the specific involvement of the left temporal pole to visual object naming, we used a lesion approach and assessed a group of patients with epilepsy associated with an epileptogenic lesion centered at the temporal pole (Abou-Hamden et al 2010;Byrne et al 2010;Kawai and Shimizu 2005;Toledano et al 2013), and a group of matched healthy controls on a visual confrontation naming task.…”

Connectivity analysis of novelty process in habitual short sleepers

“…There are two Bayesian model selection (BMS) approaches for selecting the best (optimal) model at the group-level: fixed-effect analysis (FFX) and random-effect analysis (RFX) (Boly et al, 2011;Campo et al, 2012;Friston and Penny, 2011;Stephan et al, 2009). In the FFX, the sum of the log-evidence of each subject for each model is calculated to find the optimal model with maximum summed logevidence (Stephan et al, 2009).…”