Callosal degradation in HIV-1 infection predicts hierarchical perception: a DTI study

Abstract

HIV-1 infection affects white matter circuits linking frontal, parietal, and subcortical regions that subserve visuospatial attention processes. Normal perception requires the integration of details, preferentially processed in the left hemisphere, and the global composition of an object or scene, preferentially processed in the right hemisphere. We tested whether HIV-related callosal white matter degradation contributes to disruption of selective lateralized visuospatial and attention processes. A hierarchical letter target detection paradigm was devised, where large (global) letters were composed of small (local) letters. Participants were required to identify target letters among distractors presented at global, local, both or neither level. Attention was directed to one (global or local) or both levels. Participants were 21 HIV-1 infected and 19 healthy control men and women who also underwent Diffusion Tensor Imaging (DTI). HIV-1 participants showed impaired hierarchical perception owing to abnormally enhanced global facilitation effects but no impairment in attentional control on local-global feature selection. DTI metrics revealed poorer fiber integrity of the corpus callosum in HIV-1 than controls that was more pronounced in posterior than anterior regions. Analysis revealed a double dissociation of anterior and posterior callosal compromise in HIV-1 infection: compromise in anterior but not posterior callosal fiber integrity predicted response conflict elicited by global targets, whereas compromise in posterior but not anterior callosal fiber integrity predicted response facilitation elicited by global targets. We conclude that component processes of visuospatial perception are compromised in HIV-1 infection attributable, at least in part, to degraded callosal microstructural integrity relevant for local-global feature integration.

Figure 1. Design of the local-global paradigm

3 attention blocks (1. Attend the global level, 2. Attend the local level, 3. Attend both levels) with 4 randomly intermixed conditions (global targets, local targets, both: global and local targets, neither global nor local targets) were repeatedly presented. Target letters were Es and Ts, non-target letters Fs and Ls. Subjects answered the question: “Is there an E or a T?” by pressing a Yes key for targets (E and T) and a No key for non-targets (F and L) at the attended level. Four specific component process effects were calculated:

1. Precedence: selective (SA) or divided attention (DA) block with targets at one level, i.e.,

   1. precedence (SA) = (global targets/global instruction) – (local targets/local instruction);

   2. precedence (DA) = (global targets/both instruction) – (local targets/both instruction);

2. Interference: selective and divided attention blocks with targets at both levels: congruency = incongruent trials (e.g. global T, local E) – congruent trials (global E, local E);

3. Response conflict for selective attention:

   1. global instruction block: inhibition = (local targets) – (no targets at either level),

   2. local instruction block: inhibition = (global targets) – (no targets at either level);

4. Response facilitation for selective attention:

   1. global instruction block: inhibition = (global targets) – (targets at both level),

   2. local instruction block: inhibition = (local targets) – (targets at both level);

Figure 2

Mean reaction times (RT) and standard errors (SE) for HIV-1 infected and control participants for the local-global special effects: A. Precedence effects and B. Congruency effects (incongruent=INC, congruent=CON) for selective (local, global) and divided (local+global) attention conditions. C. Response conflict and D. Response facilitation for selective (local, global) attention conditions. See Table 2 for reaction times and difference values for each local-global special effect.

Figure 3

Corpus callosum microstructural fiber integrity in HIV-1 infected individuals (HIV) and controls (CTL) measured with diffusion tensor imaging (DTI): Mean raw values and standard errors (SE) for fractional anisotropy (FA) (lower left panel), longitudinal diffusivity (λL) (upper right panel), and transverse diffusivity (λT) (lower right panel) for six callosal sectors: Genu, premotor, motor, parietal, temporal and splenium (upper left panel; figure was taken from Pfefferbaum et al., 2009).

Figure 4

Correlations between specific effects of local-global processing (left panel: response conflict, right panel: response facilitation) and DTI metrics (fractional anisotropy (FA) or longitudinal (λL) diffusivity) for genu and temporal callosal sections. CTL: controls; HIV: HIV-1 infection.