A Neural Substrate for Mirror Agnosia and Mirror Image Agnosia – Is it a Network disorder?
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.325339
Source of Support: None, Conflict of Interest: None
Keywords: Free surfer, major cognitive disorder, mirror agnosia, mirror image agnosia, network disorderKey Message: Mirror image processing deficits could be a Network Disorder.
Mirror images appear to have spatial left to right and front to back inversion. In humans, mirror image of one's own self-processing is believed to take place through a phenomenon called as mental diplopia where a person seeing his mirror image has dual representation - one for the real body schema of self and one for the reflected image. Cognitive understanding is required to recognize that the reflected image is from the opposite visual field. ,,,, When we look at our self in a mirror, it appears as if a person is standing behind the mirror at the same distance and facing us. However, in reality it is a front to back inversion, as mirrors just reflect what is in front of it and not right to left.
Mirror agnosia exists when patients face difficulty in spatially localizing the reflected image. ,, They mostly jam into the mirror in search of the object. Mirror image agnosia is the situation where patient misinterprets the reflected image as someone else though there is no error in spatial localization. ,,, We found patients with MCD who showed curious interest in the Mirrors, conversing, fighting with their images, breaking mirrors while searching for objects inside and addressing the self-face as another person. one of our patients was talking to his mirror image as if it was his nephew. His surprised spouse opened the door of the cupboard to which the mirror was fixed. When the mirror disappeared the nephew also disappeared. The patient accused family members of having murdered the nephew, resulting in serious legal problems.
We set out the following study objectives (i) to clinically evaluate if problems in mirror image processing exist in MCD; (ii) to elaborate the nature of these deficits, their association with apraxias, agnosias, and the MCD sub-type and (iii) lastly to identify its neural substrates using multi-modal structural and functional MRI brain imaging.
The study was approved by the Institute Ethics Committee and informed consent was obtained from all participants/caregivers. Patients identified as MCD according to DSM-5, aged between 30-80 years were evaluated from February 2015 to May 2017. Non-degenerative causes of dementia, other neurological or psychiatric illness were excluded. Demographic data, detailed history, and clinical examination were carried out with specific examinations for apraxia, agnosia. Specifically, visual object agnosia and prosopagnosia, mirror agnosia and mirror image agnosia, and ability to recognize reflected faces of others. Hindi Mental Status Examination (HMSE), Clinical Dementia Rating Scale, hematological workup, Vitamin B12, Thyroid functions, HIV, VDRL, LFT, RFT, and any specific risk factor assessment in individual basis was done.
Bedside Tests for reflected image processing: A 45 cm × 45 cm mirror was used. Before testing, we checked for visual acuity (corrected with glasses), ability of patient to identify and name a mirror and describe its purpose. Patient was seated comfortably on a chair and the mirror was placed in front of him/her on a table at a distance of 30 cm.
The neuropsychological tests were adapted from the NIMHANS Neuropsychological Battery and included N back test (Working memory), Digit Vigilance test (Attention), Animal names test (Category fluency), Complex figure Test – Copy trials (Visuospatial constructional ability) and Rey's Auditory Verbal Learning Test (AVLT) (Verbal learning and memory).
MRI Brain acquisition and analyses: MRI data were acquired on a Siemens Skyra 3.0 Tesla scanner with the following sequences:
Surface-based cortical reconstruction from the T1-weighted images were performed using the FreeSurfer Software Suite that employs well-validated and fully automated procedures. The fMRI preprocessing and analyses were carried out using AFNI software. The functional data were slice-time corrected, realigned to the mean-image, co-registered to T1w data using local-Pearson correlation function, and transformed to MNI template space using non-linear warp functions. A band-pass filter of 0.01-0.2 Hz was applied along with regression of motion parameters. The data was smoothed at 8 mm FWHM. For the Diffusion MRI data, the DIFFPREP module in TORTOISE V2.5.2 was used to compute distortion corrections for participant motion, eddy currents, and basic echo-planar imaging (EPI) distortions. This data was then exported to FSL (FMRIB Software Library, FMRIB, Oxford, UK) for tensor computation with weighted least squares approach and group comparisons using Tract Based Spatial Statistics (TBSS). Of the 18 subjects, 11 underwent MRI. For MRI analysis, the subjects were binned into two groups, one with mirror agnosia alone (n = 6) and the other with mirror-image agnosia with or without mirror-agnosia (n = 5). Owing exploratory nature of these analyses and the limited sample size, all results are presented at P < 0.05 (uncorrected) unless specified otherwise.
Demographic and clinical profile
18 patients were identified. Of them 61% were males. Mean age (SD) was 62.33e8.1 years and 56% of them were graduates. The MCD types included Alzheimer disease (AD) (44%), Frontotemporal dementia (FTD) (22%), Corticobasal ganglionic degeneration (CBGD) (22%) and Creutzfeldt-Jakob disease More Details (CJD) (11%). The mean duration of illness (SD) was 3.11 ± 1.39 years. The mean HMSE score (SD) was 14.83 ± 3.31 and mean CDR score (SD) 2.16 ± 0.61. The MCD was considered mild in 5% and severe in 95% using HMSE. With CDR global score, the MCD was qualified as mild in 11%, moderate in 61% and severe in 28%. During the bed-side test for reflected image processing, patients showed a special attraction and curiosity to go to mirror, misidentified self-image as God, stranger, nephew, mother and enemy soldier but identified the inanimate objects like ornaments correctly with furious fighting to get them back. Understandably, these symptoms cause serious problems to caregivers. (For a demonstration see supplementary video-1 for mirror agnosia and video-2 for mirror image agnosia.)
Mirror agnosia and Mirror image agnosia: 11 had mirror agnosia, 5 had mirror image agnosia and 2 had both. Among 11 patients with mirror agnosia: AD was seen in 8 cases, FTD in 1 case, CBGD in 1 case, and CJD in 1 case. For the 5 patients with mirror image agnosia, the conditions seen were FTD in 2 cases, CBGD in 2 cases and CJD in 1 case. Among the 2 patients that had both deficits, 1 had FTD and 1 had CBGD.
Association of mirror agnosia and mirror image agnosia with apraxias and other agnosias: Among the patients with mirror agnosia, 90% had apraxia while in patients with mirror image agnosia alone or both, apraxia was uncommon. Among the 5 patients with mirror image agnosia, 4 had prosopagnosia, 1 had visual object agnosia. Among the 2 patients with both, 1 had prosopagnosia. [[Table 1] summarizes the clinical profile].
Neuropsychological assessment results
Fourteen patients were able to complete Neuropsychological evaluation. Compared to normative references, impairments were found in all domains tested. The groups had comparable impairments across all domains except in motor speed which was more impaired in patients with mirror image agnosia. [[Table 2] summarizes the neuropsychological profile].
On visual inspection, the pattern of atrophy on the T1w structural MRI was as follows: Parietotemporal 5 (28%), Frontotemporal 2 (11%), Diffuse 8 (44%), Parietal 2 (11%) and no atrophy in 1 (6%). On morphometric analysis, between-group differences were found in cortical thickness and surface area in both hemispheres at uncorrected P value < 0.05. The results indicate that MA group had thicker cortices but reduced surface area when compared to those with mirror image agnosia, at several brain regions involving frontoparietal areas as noted in [Table 3] and shown in [Figure 2]a and [Figure 2]b.
Seed-based Resting-state fMRI
Spheres of 5 mm radius placed at bilateral angular gyrus [MNI: x = ±54, y = -56, z = 31] were chosen as seed region of interest. The whole-brain connectivity of the right angular gyrus did not reveal any significant differences between the two groups. Whereas, the left angular gyrus had increased functional connectivity with left anterior cingulate, left dorsolateral prefrontal and bilateral posterior cingulate cortex in patients with mirror agnosia group as compared to those with mirror image agnosia at P value < 0.05 and minimum 40 voxel extent (uncorrected). [Figure 2]
TBSS-based DTI results
Patients with mirror agnosia had significantly greater fractional anisotropy (FA) in the left superior longitudinal fasciculus and reduced FA in the right uncinate and inferior fronto-occipital fasciculi. [Figure 2]c and [Figure 2]d.
We examined the clinical, neuropsychological and neuroimaging patterns of MCD patients who have deficits in reflected image processing. Alzheimer's disease was the most common diagnosis in patients with mirror agnosia while non-AD dementias (FTD, CBGD, and CJD) were seen in patients with mirror image agnosia or both. Majority of patients (90%) with mirror agnosia had apraxias, while apraxia was seen in only 40% patients with mirror image agnosia. Prosopagnosia and impaired recognition of reflected faces of others was seen exclusively in patients with mirror image agnosia or both. Visual object agnosia was seen in only one patient with mirror image agnosia. Our findings of association of apraxia with mirror agnosia and prosopagnosia with mirror image agnosia support the hypothesis that mirror image agnosia could be the ventral stream dysfunction and mirror agnosia due to dorsal stream dysfunction.
There was no significant statistical difference between the patients with mirror agnosia and mirror image agnosia among neuropsychological tests other than motor speed. Mirror agnosia does not correlate with severity of disease but affects activity of daily living, as they break mirrors and injure themselves. The patients with mirror agnosia may think that vehicles seen in the mirror are in front of them which can lead to accidents.
More than 50% of patients with mirror agnosia had parietal atrophy. Diffuse atrophy was common in patients with mirror image agnosia and those with both phenomena. This was reflected in surface-based morphometric analysis results indicating that mirror agnosia group had thicker bilateral frontoparietal regions but reduced surface area in left inferior parietal and supramarginal regions when compared to mirror image agnosia group, in contrast to the loss of right parietal volume in patients with strokes.,, These differences could reflect a subtler and widespread neurodegenerative process seen in MCD compared to localized brain pathology in strokes. There was differential loss in surface area and cortical thickness which represent two biologically distinct brain processes. Greater right frontoparietal cortical thickness may offer some advantage for the mirror-agnosia group as self-recognition and object identification are both correlated with right hemispheric activity. Results suggest that bilateral frontoparietal differences play an important role in mirror agnosia, whereas mirror image agnosia could have more diffuse underlying processes.
There were differences in large-scale functional and structural brain connectivity. The left angular gyrus (AG) showed increased connectivity with anterior cingulate (salience network), dorsolateral prefrontal (executive network) and posterior cingulate cortex (default mode network) in patients with mirror agnosia alone as compared to those with mirror image agnosia. These results could indicate either a hypo-connectivity of left AG with other crucial brain network regions in mirror-image agnosia group or a compensatory hyper-connectivity of left AG in mirror agnosia group. Whether such compensatory increased connectivity could be due to disinhibition produced by disease activity in corresponding opposite regions or enhancement due to dysfunctional plasticity needs larger studies., The DTI results show that there are bi-hemispheric differences in the micro-structural integrity of the major white-matter pathways. The FA measure was found to be significantly greater in the superior longitudinal fasciculus on the left side and on the right side there was reduced FA in uncinate and inferior-fronto-occipital fasciculus for patients with mirror agnosia which is consistent with functional connectivity findings of bi-hemispheric networks alterations. All three pathways that were found to be different are major association bundles that connect the frontal, occipital, parietal, and temporal lobes. Given that there are bi-hemispheric alterations in structural and functional connectivity a possibility of these phenomena being a network disorder cannot be excluded. These data need further evaluation and could generate insight into the ways interactions of different brain regions lead to different clinical neuropsychiatric symptoms.
Lots of visuomotor transformations is needed to locate the reflections to its source and recognize the virtual and real differently. Menon et al., hypothesized that mirror agnosia is due to a dysfunction of the right parietal cortex. Binkofski et al. related right tempero-parieto-occipital region to 'mirror agnosia'. Our study establishes that deficit in processing reflected images leading to mirror agnosia and mirror image agnosia can also occur in MCD. However, the phenomena do not appear to be disease specific as it is seen several types of dementia.
The sample size was small as the phenomena is relatively rare. All patients were not amenable for complete work up. Control group of patients without mirror phenomena or healthy controls were not recruited.
This study provides comprehensive clinical, neuropsychological, and brain-imaging profile of mirror agnosia and mirror image agnosia phenomena in patients with MCD, whereas previously available literature is in patients with strokes, trauma and tumors. The results indicate that these deficits are likely to be domain specific and not disease specific. Neuroimaging results provide novel insights regarding the possibility of involvement of both specific regions and as well as large scale-networks in reflected image processing and its breakdown in disease states.
We acknowledge with Gratitude our patients and care givers who Cooperated for this work, Our Director for all encouragements.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]