Visual Personal Familiarity in Amnestic Mild Cognitive Impairment

BACKGROUND: Patients with amnestic mild cognitive impairment are at high risk for developing Alzheimer's disease. Besides episodic memory dysfunction they show deficits in accessing contextual knowledge that further specifies a general concept or helps to identify an object or a person. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, we investigated the neural networks associated with the perception of personal familiar faces and places in patients with amnestic mild cognitive impairment and healthy control subjects. Irrespective of stimulus type, patients compared to control subjects showed lower activity in right prefrontal brain regions when perceiving personally familiar versus unfamiliar faces and places. Both groups did not show different neural activity when perceiving faces or places irrespective of familiarity. CONCLUSIONS/SIGNIFICANCE: Our data highlight changes in a frontal cortical network associated with knowledge-based personal familiarity among patients with amnestic mild cognitive impairment. These changes could contribute to deficits in social cognition and may reduce the patients' ability to transition from basic to complex situations and tasks

Age and the Neural Network of Personal Familiarity

BACKGROUND: Accessing information that defines personally familiar context in real-world situations is essential for the social interactions and the independent functioning of an individual. Personal familiarity is associated with the availability of semantic and episodic information as well as the emotional meaningfulness surrounding a stimulus. These features are known to be associated with neural activity in distinct brain regions across different stimulus conditions (e.g., when perceiving faces, voices, places, objects), which may reflect a shared neural basis. Although perceiving context-rich personal familiarity may appear unchanged in aging on the behavioral level, it has not yet been studied whether this can be supported by neuroimaging data. METHODOLOGY/PRINCIPAL FINDINGS: We used functional magnetic resonance imaging to investigate the neural network associated with personal familiarity during the perception of personally familiar faces and places. Twelve young and twelve elderly cognitively healthy subjects participated in the study. Both age groups showed a similar activation pattern underlying personal familiarity, predominantly in anterior cingulate and posterior cingulate cortices, irrespective of the stimulus type. The young subjects, but not the elderly subjects demonstrated an additional anterior cingulate deactivation when perceiving unfamiliar stimuli. CONCLUSIONS/SIGNIFICANCE: Although we found evidence for an age-dependent reduction in frontal cortical deactivation, our data show that there is a stimulus-independent neural network associated with personal familiarity of faces and places, which is less susceptible to aging-related changes

Relative increases in brain activity associated with personal familiarity.

<p>All activations are significant at p<0.05, corrected for multiple comparisons at the cluster level (with a height threshold of p<0.001, uncorrected at the voxel level). For each region of activation, the coordinates of the maximally activated voxels within the activation cluster are given in standard stereotactic MNI space. FF: familiar faces, UF: unfamiliar faces, FP: familiar places, UP: unfamiliar places; # indicates that this activation maximum is part of the same cluster.</p

Demographic and neurocognitive characteristics.

1<p>age-adjusted z-values unless otherwise indicated.</p>2<p>effect size measure (Cohen's d).</p><p>BDI: Beck Depression Inventory; MMSE: Mini Mental State Examination; CVLT: California Verbal Learning Test; WMS-R: Wechsler Memory Scale – Revised; FAS: Controlled Oral Word Association Test, letters F,A,S; AAT: Aachen Aphasia Test.</p

Within-group effect of personal familiarity irrespective of stimulus type.

<p>The figure shows brain areas with relative increase in neural activity for both subject groups when perceiving familiar>unfamiliar stimulus content irrespective of stimulus type. The local maxima are superimposed on a rendered standard single subject brain provided by SPM5. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020030#pone-0020030-t003" target="_blank">Table 3</a> for exact coordinates. R = right, L = left, A = anterior, P = posterior.</p

fMRI paradigm.

<p>This figure visualizes one experimental run of the fMRI paradigm. Three of these runs, each lasting 352 s, were performed. The order of the four conditions (FF, UF, FP, UP) was counterbalanced across the runs. Each block (35 s) of a condition consisted of a visual stimulus presented from five different angles (S1-5), a familiarity question (Q), and a response (“thank you”, R). FF = familiar face, UF = unfamiliar face, FP = familiar place, UP = unfamiliar place, B = baseline (fixation cross, 9 s).</p

Interaction between age and familiarity.

<p>The figure shows an area (anterior cingulate cortex, −3, 39, 3) in which the young but not the elderly subjects showed reduced neural activity for unfamiliar versus familiar stimuli irrespective of stimulus type. Signal change at the local maximum is statistically significant at the voxel level (Psvc<0.05) in a ROI analysis based on the coordinates by <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015790#pone.0015790-Sugiura3" target="_blank">[29]</a>. The local maximum is superimposed on a sagittal single subject brain section provided by SPM5. The histogram displays percentage BOLD signal change for the local maximum as a function of the experimental conditions (mean and 90% confidence interval). YF = young familiar, YU = young unfamiliar, EF = elderly familiar, EU = elderly unfamiliar.</p

Relative increases in brain activity associated with personal familiarity.

<p>All activations are significant at p<0.05, corrected for multiple comparisons at the cluster level (with a height threshold of p<0.001, uncorrected at the voxel level).</p><p>* = p_SVC<0.05 in a hypothesis-driven region-of-interest (ROI) analysis. For each region of activation, the coordinates of the maximally activated voxels within the activation cluster are given in standard stereotactic MNI space. FF: familiar faces, UF: unfamiliar faces, FP: familiar places, UP: unfamiliar places;</p><p># indicates that this activation maximum is part of the same cluster.</p

Demographic and clinical characteristics.

<p>MMSE, Mini Mental State Examination; CDR, Clinical Dementia Rating; WMS-R,</p><p>Wechsler Memory Scale – Revised; COWAT, Controlled Oral Word Association Test; CVLT, California Verbal Learning Test;</p><p>*p<0.05, 2-tailed.</p