Bilateral hippocampal dysfunction in schizophrenia

Abstract

The hippocampus has long been known to be important for memory, with the right hippocampus particularly implicated in nonverbal/visuo-spatial memory and left in verbal/narrative or episodic memory. Despite this hypothesized lateralized functional difference, there has not been a single task that has been shown to activate both the right and left hippocampus differentially, dissociating the two, using neuroimaging. The transverse patterning (TP) task is a strong candidate for this purpose, as it has been shown in human and nonhuman animal studies to theoretically and empirically depend on the hippocampus. In TP, participants choose between stimuli presented in pairs, with the correct choice being a function of the specific pairing. In this project, TP was used to assess lateralized hippocampal function by varying its dependence on verbal material, with the goal of dissociating the two hippocampi. Magnetoencephalographic (MEG) data were collected while controls performed verbal and nonverbal versions of TP in order to verify and validate lateralized activation within the hippocampi. Schizophrenia patients were evaluated to determine whether they exhibited a lateralized hippocampal deficit. As hypothesized, patients’ mean level of behavioral performance was poorer than controls’ on both verbal and nonverbal TP. In contrast, patients had no decrement in performance on a verbal and nonverbal non-hippocampal-dependent matched control task. Also, controls but not patients showed more right hippocampal activation during nonverbal TP and more left hippocampal activation during verbal TP. These data demonstrate the capacity to assess lateralized hippocampal function and suggest a bilateral hippocampal behavioral and activation deficit in schizophrenia.

Cognitive impairments in psychotic disorders: common mechanisms and measurement

“…Recent work on relational memory encoding and retrieval has shown evidence for impaired DLPFC function associated with impaired relational memory function (98) and autobiographical memory (99) in schizophrenia, though other recent work has also implicated hippocampal function (100).…”

The case for a dual-process theory of transitive reasoning

“…Here, training was via auditory and visual signals from the mother hen and the relational comparative was food-location preferences along a linear transitive dimension. Humans also have transitivity lateralised to the right hemisphere, so long as the task is not a fully verbal one and the participant is typically-developing (e.g., does not have schizophrenia - Hanlon et al, 2011).…”

“…Other FMRI studies have confirmed with stimuli from geometric shapes to faces, that the hippocampus as critical to the relational reasoning required for inferring transitive responses when testing follows extensive training (Dickins & Dickins, 2001;Wendelken & Bunge, 2009). The critical importance of the hippocampus in human transitive reasoning has been further corroberated by MEG studies with humans (Hanlon et al, 2011) and PET studies on human participants (Nagode & Pardo, 2002).…”

Dynamic Imaging of Deep Brain Structures with MEG: Contributions to Understanding Human Memory

“…(e.g. Alvarado & Bachvallier, 2005;Astur & Constable, 2004;Driscoll et al, 2003;Hanlon et al, 2003Hanlon et al, , 2005Hanlon et al, , 2011Meltzer et al, 2008, Moses, Ostreicher, Rosenbaum & Ryan, 2008Moses et al, 2009;Rickard & Grafman, 1998;Rickard, Verfaellie & Grafman, 2006;Reed & Squire, 1996;Ostreicher, Ryan, Moses & Rosenbaum, 2010;Saksida et al, 2007). The transverse patterning task is structurally analogous to the childhood game "rock-paperscissors" (Rock crushes Scissors, Scissors cut Paper, Paper covers Rock), but uses novel stimuli (A, B, C) that have ambiguous meanings outside the context of their pairings (A beats B, B beats C, C beats A; or A+B-, B+C-, C+A-; Fig.…”

“…The work of Hanlon et al (2003Hanlon et al ( , 2005Hanlon et al ( , 2011 demonstrates that in adults with hippocampal dysfunction, recruitment of the hippocampus bilaterally may support performance for a task that typically elicits unilateral activation. However, it is unclear whether this effect may be found in developmental populations, since children show different laterality patterns than adults.…”