Given our finding of normal-SPD differences in SWM, Pearson's correlations were calculated for these groups to examine the association between DLPFC/VLPFC volume and task performance. All of the following correlational analyses controlled for age and education. Among the healthy control participants but not the SPD patients, fewer errors on the SWM test was associated with larger gray matter volume: right BA44 (HC: r = -0.89, p < 0.005, ; SPD: r = 0.04, p = ns; HC vs SPD, Fisher's Z test = -3.86, p < 0.01) and right BA45 (HC: r = -0.68, p < 0.01; SPD: r = -0.02, p = ns; HC vs SPD, Fisher's Z test = -2.14 p < 0.05). The association between right BA44 and SWM in HCs survived the Bonferroni correction of 0.0025, but the relation between BA45 and SWM in HCs did not.
Individual differences in right BA 44 volume and spatial working memory errors
In order to see if there was utility in PFC volumes predicting SWM performance, we also calculated the correlation coefficient for the entire sample of HC and SPD participants, given that they showed significant differences in SWM performance. The correlation coefficient was significant conventionally (but did not survive Bonferroni correction of 0.0025) and, as expected, greater right BA44 volume was associated with better SWM performance (see ; r = -0.45, p = 0.009).
Correlations between SWM performance, DLPFC/VLPFC gray matter volume and clinical symptomatology (as assessed by interview and self report) for SPD patients did not reach significance.
The first novel finding of this study is that patients with SPD demonstrate visual-spatial working memory impairment relative to BPD patients and HC. These results add to previous work by suggesting that SWM abilities may help differentiate SPD patients from BPD. SWM may thus represent a core neuropsychological deficit in SPD [8
] and potentially serve as an important biomarker for differentiating between personality disorders. The second major finding is that, consistent with our hypothesis, larger volume of right BA44 was associated with better task performance (fewer errors) in HC but not in the SPD group alone, the diagnostic group that showed significantly impaired performance. However, the association between larger right BA 44 volume and better SWM was observed across the HC-SPD spectrum.
Our finding of visual-spatial working memory impairment in SPD patients is consistent with prior work [7
] as well as studies involving schizophrenia patients [51
] thought to evidence similar genetic, neurobiological and neuropsychological abnormalities as those with SPD [53
]. Although some previous studies report intact visual-spatial working memory in individuals with BPD [16
], a few studies have reported BPD deficits in this domain [18
]. However, much of this work included BPD patients who met criteria for other Axis II disorders, including SPD, thus rendering it difficult to establish a clear neurocognitive profile for BPD. The present study addressed these comorbidity issues by including BPD patients without SPD traits (i.e. no more than three SPD diagnostic criteria with two items rated as 1.0 (definitely present) and one item rated as 0.5 (somewhat present)) and SPD patients without BPD traits. Taken together, our findings indicate SPD but not BPD patients exhibit SWM deficits and underscore the diagnostic specificity of this deficit.
SPD patients demonstrated a specific type of spatial working memory deficit in this study, involving a high number of erroneous returns to previously searched locations. On the ‘Strategy Use’ score, however, SPD patients performed within normal limits. These findings suggest that SPD patients can adopt a spatial-search strategy, but it does not aid in the accuracy of their performance. Thus, while caution is necessary in drawing conclusions from these results, it is possible to argue that SPD erroneous re-visits to boxes where they previously had found tokens may be better attributed to difficulties in executive functioning, such as perseverative behavior and/or temporary storage and/or manipulation of spatial and/or visual information deficits [57
], rather than impairments in strategy use. Consistent with this idea, Raine and colleagues [36
] reported that individuals with high scores on schizotypal personality measures demonstrated more perseverative errors on an executive functioning task. Further research is needed to understand executive functioning difficulties in SPD patients and potential ways in which cognitive interventions, e.g., cognitive remediation and/or training in strategy-use abilities might improve function.
The present study's visual-spatial working memory task and its measures of errors and strategy use have been shown to be primarily sensitive to frontal-lobe functioning [58
]. Additionally, Petrides and colleagues [59
] have proposed that working memory processes can be mapped onto two distinct cytoarchitectonic regions—VLPFC, where information is maintained in working memory, and DLPFC, where information is monitored and manipulated in working memory [61
]. Consistent with the above-mentioned research, as well as animal and human work demonstrating dorsolateral and ventral prefrontal cortex involvement in spatial working memory [23
], this study showed that larger right BA44 volume was associated with better spatial working memory performance in HC. This same relationship was not observed in the SPD group alone. Given these findings, it is important to note our most recent paper reporting brain volume in this same sample [39
] did not detect SPD-HC group differences in VLPFC (i.e. BA44) volume. Although some prior work suggests VLPFC volumetric abnormalities in SPD individuals [35
], our failure to find group differences in this region is not entirely surprising given our previous work [34
] and other research reporting no SPD-HC prefrontal volume differences, suggesting these regions may be relatively preserved in SPD individuals [53
]. However, in the absence of group differences in prefrontal volume, the current study's correlational results across the HC-SPD spectrum suggest there is an association between volume and neurocognitive performance. Our data provide support for the new NIMH Research Domain Criteria (RDoC) strategic plan which calls for studies to classify psychopathology based on dimensions of “observable behavior and neurobiological measures.”
Although this study did not include fMRI to determine whether SPD patients demonstrate dysfunctional prefrontal cortex activation during spatial working memory processing, our previous imaging work implicates disrupted right BA44 and BA45 function in SPD patients during visual-spatial working memory tasks [31
]. Koenigsberg and colleagues [31
] demonstrated that HC showed increased activation in right BA44/45/47, bilateral premotor areas (BA6), as well as additional parietal regions during a visual-spatial working memory task. SPD patients, on the other hand, showed reduced activation during the maintenance period of a visual-spatial working memory task in left BA44/45/47/10, left intraparietal cortex, and left posterior inferior gyrus. Importantly, our prior finding of an SPD-related deficit in right BA44/45 activation [31
] is consistent with our current finding of a lack of association between volume of BA44 and SWM performance in SPD. One potential explanation for our results may be differential recruitment of the neuronal network subserving this function in SPD patients. For example, research in HC provides evidence of VLPFC (i.e. BA44/45) connections with posterior sensory association areas [59
] and reports VLPFC's role in the process of maintaining visual information in working memory [63
]. It is also significant that our results were localized to the right hemisphere, consistent with research linking hemispheric lateralization with type of task, (i.e. spatial with right, verbal with left) [59
Our study has several limitations. First, given the constraints of the task, we were not able to offer greater specificity regarding the exact component of spatial working memory that is impaired in SPD patients. For example, our prior study [31
] reported that during the encoding and maintenance period of a SWM task, HC showed increased activation in right BA44/45/47, among other prefrontal and parietal regions. In contrast, SPD patients showed decreased activation in left BA44/45/47 and other regions during this same period of maintaining the spatial locations in memory. Taken together with these findings and evidence of BA44/45 involvement in maintenance functions in HC [63
], we can only speculate that SPD patients experience difficulty during the maintenance period in particular but cannot offer evidence to support this idea. Future research needs to investigate potential SWM deficits in greater detail and ideally include a spectrum sample examining HC, SPD, and schizophrenia patients. Also, despite the present study's significant results, the findings need to be replicated in a larger sample, and it would be beneficial to include a group of schizophrenia patients to examine the full schizophrenia spectrum. Lastly, research suggests that stress, which is thought to play an important role in the etiology and course of personality disorders, may impair prefrontal cortex working memory performance in humans and animals [65
]. Thus, further research examining the effect of stress on prefrontal cortex functioning in BPD and SPD patient groups would help better characterize SWM abnormalities in these disorders.
The present study's findings highlight visual-spatial working memory deficits in SPD patients and, given the complexity of personality disorder groups and their many overlapping and diverging aspects, suggest that SWM may be a potential biomarker for differentiating among/between them. Also, given our finding of a relation between prefrontal cortex volume and SWM performance, these results suggest the need to further investigate functional prefrontal correlates of different working memory tests and how they may or may not contribute to cognitive, behavioral and emotional disturbances that may underpin SPD and BPD traits, respectively. Use of the SWM test in personality disorder studies examining change with treatment may help, and baseline predictors of treatment response may be fruitful.