Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
3:00 PM
Background: Recognition of faces/face emotions is commonly impaired in adults/children with autism. Given the importance of face processing in autism, the ability to measure face-processing pathways with DTT (Smith et.al., 2009, JMRI), and the potential of pathway abnormalities to produce strong behavioral effects, we tested for abnormalities in face-processing pathways in autism. In an initial study (Conturo et.al., 2008, JINS), the right hippocampo-fusiform (HF) pathway involved in face recognition had reduced minimum-diffusivity (D-min, intrinsic across-fiber diffusivity; Smith et.al., 2009).
Objectives: Characterize/interpret DTT abnormalities in face-processing pathways by comparison to sensitive neuropsychological tests (NPTs).
Methods: Custom diffusion-tensor MRI data were acquired in 17 participants with high-functioning autism meeting ADOS/ADI criteria (age 16-53) and 17 individually-matched controls from 2002-2006. For comparison, we acquired sensitive custom NPTs of: face-memory (Best et.al., IMFAR2009); face-gender identification (Wilkinson et.al., IMFAR2009); and face-emotion recognition (Rump et.al., 2009) in the autism participants. We also examined the relationship to symptom severity during development as measured by the ADI.
Results: Autism participants were separated into lower/higher face-recognition subgroups using face-memory and Benton NPTs. The lower-performance subgroup had significantly slower D-min in both right HF (p = 0.019) and right amygdalo-fusiform (AF) pathway (p = 0.011). Gender/emotion NPTs showed a strong relation to DTT for both right HF/AFpathways. The DTT-NPT correlation was very high (e.g., r = 0.995/0.463 without/with one outlier; AF vs. face-gender NPT). All NPTs showed the same relation of slower D-min with lower performance for both pathways, indicating that the D-min reduction in autism-vs-controls described in (Conturo, et al., 2008) is functionally significant. The unusual reversal of the expected DTT-NPT relation supports a mechanism of small-diameter axons in right AF/HF. This interpretation parsimoniously accounts for the reversed DTT-NPT relation because small-diameter axons have slower transmission speed. This biologic mechanism is also consistent with: small cell bodies in hippocampus (Bauman et.al., 2005) and minicolumns (Casanova et.al., 2002); reduced fMRI correlations (Just et.al., 2004; Kleinhans et.al., 2008); lengthened reaction times (Townsend et.al., 1996); slowed electrophysiology (McPartland et.al., 2004); and symptom abatement with fever (Curran et.al., 2007). A correlation between ADI, Section A (reciprocal social interactions) and right HF D-min (r = -0.413; p = 0.047; slower D-min associated with childhood social impairment) suggests an early-developmental process, consistent with known impairments in face processing in young children. The D-min reduction is unlikely to be due to intervening variables (e.g., behavioral therapy) since participants do not report any consistent therapy. Any therapy effects would thus average out (and would oppose the reversed DTT-NPT relation). Finally, the high DTT-NPT correlation suggests that axonal diameter is a strong determinant of function, despite intervening variables. [More subtle secondary changes can occur in left AF/HF (Conturo et.al, 2008), consistent with relative sparing of object processing in autism (Humphreys et.al., 2008).]
Conclusions: A strong association between decreased D-min and decreased function (as measured by behavioral NPTs) occurred in right AF/HF in autism, supporting a mechanism of small-diameter axons. A similar DTT-ADI relation was found, suggesting that this mechanism occurs in childhood, and persists into adulthood.
Objectives: Characterize/interpret DTT abnormalities in face-processing pathways by comparison to sensitive neuropsychological tests (NPTs).
Methods: Custom diffusion-tensor MRI data were acquired in 17 participants with high-functioning autism meeting ADOS/ADI criteria (age 16-53) and 17 individually-matched controls from 2002-2006. For comparison, we acquired sensitive custom NPTs of: face-memory (Best et.al., IMFAR2009); face-gender identification (Wilkinson et.al., IMFAR2009); and face-emotion recognition (Rump et.al., 2009) in the autism participants. We also examined the relationship to symptom severity during development as measured by the ADI.
Results: Autism participants were separated into lower/higher face-recognition subgroups using face-memory and Benton NPTs. The lower-performance subgroup had significantly slower D-min in both right HF (p = 0.019) and right amygdalo-fusiform (AF) pathway (p = 0.011). Gender/emotion NPTs showed a strong relation to DTT for both right HF/AFpathways. The DTT-NPT correlation was very high (e.g., r = 0.995/0.463 without/with one outlier; AF vs. face-gender NPT). All NPTs showed the same relation of slower D-min with lower performance for both pathways, indicating that the D-min reduction in autism-vs-controls described in (Conturo, et al., 2008) is functionally significant. The unusual reversal of the expected DTT-NPT relation supports a mechanism of small-diameter axons in right AF/HF. This interpretation parsimoniously accounts for the reversed DTT-NPT relation because small-diameter axons have slower transmission speed. This biologic mechanism is also consistent with: small cell bodies in hippocampus (Bauman et.al., 2005) and minicolumns (Casanova et.al., 2002); reduced fMRI correlations (Just et.al., 2004; Kleinhans et.al., 2008); lengthened reaction times (Townsend et.al., 1996); slowed electrophysiology (McPartland et.al., 2004); and symptom abatement with fever (Curran et.al., 2007). A correlation between ADI, Section A (reciprocal social interactions) and right HF D-min (r = -0.413; p = 0.047; slower D-min associated with childhood social impairment) suggests an early-developmental process, consistent with known impairments in face processing in young children. The D-min reduction is unlikely to be due to intervening variables (e.g., behavioral therapy) since participants do not report any consistent therapy. Any therapy effects would thus average out (and would oppose the reversed DTT-NPT relation). Finally, the high DTT-NPT correlation suggests that axonal diameter is a strong determinant of function, despite intervening variables. [More subtle secondary changes can occur in left AF/HF (Conturo et.al, 2008), consistent with relative sparing of object processing in autism (Humphreys et.al., 2008).]
Conclusions: A strong association between decreased D-min and decreased function (as measured by behavioral NPTs) occurred in right AF/HF in autism, supporting a mechanism of small-diameter axons. A similar DTT-ADI relation was found, suggesting that this mechanism occurs in childhood, and persists into adulthood.