Using diffusion-weighted imaging (DWI), we have succeeded in studying the involvement of the fornix in recognition memory. Individual differences in the white matter microstructure of this tract, particularly in the tail region, were found to reflect variation in recollection but not familiarity memory on two recognition tasks when behavior was modeled by a dual-process model of recognition memory (DPSD)(Yonelinas, 1994
). There was no significant relationship between fornix microstructure and memory performance when behavior was modeled by a unitary model of recognition memory (UVSD)(Wixted, 2007
), nor performance on two non-mnemonic tasks (color discrimination and attention).
The current study supports the idea that there are distinct MTL-medial diencephalon pathways that mediate different memory processes (Aggleton and Brown, 1999
). As the fornix is comprised predominantly of hippocampal connections, our data underline the suggestion that the hippocampal-diencephalon pathway does not play a general role in recognition memory but is particularly important for recollection (Aggleton and Brown, 1999
; Eichenbaum et al., 2007
). Our findings are consistent with reports of a role for the hippocampus in recollection but not familiarity memory (Yonelinas et al., 2002
; Davachi et al., 2003
; Ranganath et al., 2004
; Aggleton et al., 2005
) and disagree with the suggestion that memory strength is a more critical determinant of MTL involvement in recognition (Squire et al., 2007
). The present data also support work that has associated fornix and medial diencephalic damage in human amnesic patients with disproportionate impairment in recollection (Tsivilis et al., 2008
; Vann et al., 2009
) but, importantly, adds to these studies by identifying, for the first time, the involvement of the fornix without potential influences from neighboring structures (e.g. mamillary bodies) that are commonly also damaged in amnesic cases.
Interestingly, we found an effect of stimulus type, with a more significant relationship between fornix fractional anisotropy (FA) and scene recollection memory than that between fornix FA and object recollection. This is not surprising since the hippocampus Is critical for spatial cognition (O’Keefe and Nadel, 1978
). Indeed, recent work has suggested that stimulus type (objects/scenes) may be a more important determinant of MTL involvement than process type (recollection/familiarity) in recognition memory, with reports of impaired scene but intact face recognition memory in patients with hippocampal damage (Cipolotti et al., 2006
; Taylor et al., 2007
; Bird et al., 2008
). At first glance, our findings do not fit entirely with this view: there was no significant relationship between scene familiarity memory and fornix FA, and better object recollection was associated with improved fornix microstructure. It is possible, however, that our results can be reconciled to a stimulus-dependent view by considering the relationship between recollection and spatial cognition. Recollection is defined by the remembering of contextual information and as such, may often be associated with greater spatial processing, irrespective of the stimulus material presented. Likewise, a familiarity trace for a spatial scene may only require minimal spatial processing of that scene and thus, may occur independently from the hippocampus. The relationship between stimulus type and mnemonic process is undoubtedly complex (see Diana et al., 2007
; Bird and Burgess, 2008
) and requires much investigation if functional specialization within the MTL is to be fully understood.
Due to the orientation and narrow dimensions of the fornix, the use of DWI and tract-based spatial statistics (TBSS) to study this tract can be prone to partial volume errors affecting the estimation of FA at a voxel level. We conducted a number of complementary analyses to ensure that any significant findings were related to FA, and thus white matter microstructure, in the fornix only. First, any significant TBSS clusters at a group level were deprojected back into individual subject space so that any projection errors from neighboring tracts could be identified and their contribution removed. Second, probabilistic tractography was used to identify each participant’s fornix, from which mean FA was extracted and correlated with the acquired behavioral measures. Finally, white matter VBM was conducted to investigate whether any significant TBSS results could be accounted for, at least partially, by individual differences in gross fornix morphology. Critically, the findings from all three approaches were highly consistent. Both TBSS and the extraction of mean FA from individual fornices implicated FA in the fornix tail as being significantly related to recollection but not familiarity memory. Moreover, differences in fornix morphology were not found to be related to recollection memory performance.
The current results support a previous study that reported preliminary evidence for a significant correlation between fornix FA and performance on a standard memory task (Doors and People Test) in 11 healthy participants (Nestor et al., 2007
). Critically, our findings build considerably upon this by identifying the specific mnemonic processes that the fornix may be important for in a large group of participants.
As with most correlational analyses, the causal direction of our findings is unclear. It is possible that the inherent existence of better fornix microstructure is underlying improved recollection memory in some participants. Conversely, it is feasible that the utilization and improvement of recollection in individuals over time may lead to an enhancement in fornix microstructure. Regardless of this, the biological interpretation of our data requires consideration. FA is believed to reflect axon density, myelination and diameter (Beaulieu, 2002
). The degradation of white matter microstructure, particularly myelination, with ageing has been suggested to contribute to cognitive decline by reducing axonal conduction speeds and disrupting the function of neuronal networks (Peters, 2002
). It is possible, therefore, that improved fornix microstructure in neurologically healthy individuals may lead to more efficient transfer of information between the hippocampus and medial diencephalon and subsequently, other structures involved in recollection (Fields, 2008
). This, in turn, may lead to enhanced encoding and retrieval of information across neural circuits, resulting in better recollective memory.
Although FA in the fornix tail was particularly implicated in this study as correlating with recollection, there was a significant relationship between mean FA across the entire fornix and scene recollection. Consequently, it is unlikely that only white matter microstructure in the fornix tail is critical for recollection. Instead, FA in the fornix tail varied to a greater extent in our study and thus, surpassed the statistical threshold we adopted in our TBSS analyses. The tail section is perhaps one segment of the fornix that contains the highest density of fibers due to its relatively narrow dimensions (e.g. compared to the fornix body). Since FA is sensitive to fiber complexity and compression, it is conceivable, therefore, that FA values in the fornix tail are more likely to fluctuate to a larger degree across individuals.
To summarize, we have used DWI to demonstrate that the involvement of the fornix in memory tasks is significantly greater for recollection than for familiarity. This finding lends support to the notion that distinct recognition processes are subserved by different MTL and diencephalic structures.