Overview on the aims, methods and findings of the present study

In the present study, we hypothesize that BIID has a predominantly neurological basis, rooting in a deficient representation of the undesired limb and/or in a disturbed multisensory integration in cortical and subcortical areas (Blanke et al., 2009; Brang et al., 2008; Hilti & Brugger, 2010; McGeoch et al., 2011). These dysfunctional processes may derange the regular correspondence between the normally developed physical body and the feeling of belonging, what might trigger the amputation desire in individuals with BIID.

Hence, the aim of this thesis was to investigate, whether the unwanted limb in individuals with BIID is misrepresented and/or whether the multisensory information of this unwanted limbs is disrupted. In this respect we particularly envisaged the right parietal lobe and connected brain areas. As far as we know, the present thesis constitutes the first and so far largest experimental study with individuals with BIID and healthy controls. We examined bodily processes on different integration levels using clinical examinations, behavioral experiments and magnetic resonance imaging (MRI; for an overview of the study see table 15).

With respect to behavioral experimentation, up to now no behavioral task capturing the essentials of the condition were known. Our aim was thus to explore BIID with paradigms well-established in the literature on body research and to adapt them to the largely unexplored target stimulus "foot/leg". Note that, if an extremity is the target of present-day experimental research, it is commonly the hand or arm. To prevent side effects of laterality (e.g., judgments for left and right feet) in behavioral experiments we specifically reported findings of homogenous subgroups of people with BIID with a left-leg amputation desire and right handedness/footedness, even if all subjects performed all tasks.

In the following sections our findings for all three kinds of investigations – clinical, behavioral, structural imaging – will be shortly explained and discussed. Corresponding hypotheses, methodological key points and major finding(s) are summarized in table 15.

3. General Discussion

Chapter Investigation Involved

multi- sensory information

BIID group (within) compared to control group (between)

Hypotheses for BIID group Findings

Clinical Examinations

2.2.2 Neuropsychological

examination (e.g., attention and memory functions, using paper pencil and computer tasks)

15 subjects with BIID (9 left leg, 2 right leg, 4 both legs)

(within)

15 controls (between)

1) No differences

2) Reduced cognitive switching

performance (see 2.3.2) in those subjects with BIID, who have enhanced

obsessive-compulsive traits in the psychiatric examination

1) Normal cognitive functions in BIID group 2) No reduced cognitive switching performance by the subgroup with obsessive-compulsive traits to an above-median extent

No differences between groups

2.2.3 Neurological

examination (e.g., sensory and motor functions, including positions sense and vestibular functions)

15 subjects with BIID (9 left leg, 2 right leg, 4 both legs

(within)

15 controls (between)

Normal neurological status examination No differences between limb

Normal neurological status examination No differences between limb

No differences between groups

2.2.4 Psychiatric examination (e.g., assessing possible psychiatric disturbance or co- morbidities, using interview and questionnaires)

15 subjects with BIID (9 left leg, 2 right leg, 4 both legs

(within)

15 controls (between)

1) Normal psychiatric functions 2) Elevated scores in instruments assessing obsessive-compulsive signs

1) Normal psychiatric functions in BIID group 2) No differences in obsessive-compulsive traits

No differences between groups Table 15: Overview on subjects, hypotheses and findings for all investigations in the study

3. General Discussion

Chapter Investigation Involved

multi- sensory information

BIID group (within) compared to control group (between)

Hypotheses for BIID group Findings

Behavioral experiments (mostly subgroups with homogenous amputation desire and handedness/footedness)

2.3.1 _{Mental rotation Visual,}

motor, proprio- ceptive (single body parts)

8 subjects with BIID (left leg)

(within)

Compared to 8 controls (between)

Prolonged RTs for left feet, especially in unnatural positions

No difference between left and right feet in BIID group

No difference between groups for feet

2.3.2 Body transformation

and task switching

Visual, motor, proprio- ceptive; maybe some emotional aspects (whole body)

7 subjects with BIID (left leg)

(within)

Compared to 7 controls (between)

1) Faster RTs for figures with a left leg amputation

2) Reduced switching performance in those subjects with enhanced obsessive- compulsive traits

1) No difference between left and right amputated figures in BIID group

2) No reduced cognitive switching performance in BIID (no OCD)

1) Trend for faster RTs to left leg amputation (BIID group compared to control group) 2) BIID group faster switching performance than control group

2.3.3 Rubber foot illusion

(RFI)

Visual, tactile, proprio- ceptive

8 subjects with BIID (left leg)

(within)

Larger illusion for the left rubber foot in all three measurements, assessing: 1) perceived vividness of illusion

(questionnaire) 2) proprioceptive drift 3) skin temperature

1) No difference in perceived vividness of illusion between left and right foot in BIID group 2) No difference in proprioceptive drift between left and right foot in BIID group

3) No difference in skin temperature changes between left and right foot in BIID group.

3. General Discussion

Chapter Investigation Involved

multi- sensory information

BIID group (within) compared to control group (between)

Hypotheses for BIID group Findings

[continuation of the Rubber foot illusion (RFI)]

Compared to 8 controls (between)

1) No difference in perceived vividness of illusion between groups for feet

2) Trend for larger proprioceptive drifts in BIID group, but for both feet

3) Trend for larger temperature drop in BIID, but for both feet

2.3.4 Caloric vestibular stimulation (CVS) Vestibular, spatial, proprio- ceptive

13 subjects with BIID (mixed legs)

resp. 8 (left leg) (within)

Compared to 13 resp. 8 controls

(between)

1) Alleviation of the amputation desire during left-ear CVS

2) Increased skin temperature in the unwanted leg due to 1)

1) No alleviation of the amputation desire 2) No increased skin temperature on the unwanted leg in BIID group of 13 resp. of 8 subjects

2) No relevant group difference of skin temperature change for proximal and distal locations on the legs.

2.3.5 Temporal order judgments (TOJ) Tactile, temporal, spatial, proprio- ceptive

5 (four left leg and one right leg)

(within)

Differential temporal-order integration of touch below and above the desired line of amputation

Faster spatio-temporal integration on unwanted

body part (belowdesired line of amputation)

compared to the accepted body part (above desired line of amputation)

Magnetic resonance imaging (MRI) investigation

2.4 Surface-based

morphometry (cortical thickness, surface area and volume

15 subjects with BIID, (mixed legs) and 15 controls (between)

Focus on right parietal, right insular and subcortical areas known to process low- and high level information about body parts, including legs

Reduced cortical grey matter in: - right SPL (cortical thickness)

- right SI, SII and AIC (cortical surface area) - bilateral putamina (subcortical volume)

3. General Discussion