Differential effect of alcoholism and HIV infection on visuomotor procedural learning and retention.

Selective memory processes are differentially compromised in chronic alcoholism (Fein et al., 2006; McGlinchey et al., 2005; Nixon et al., 1995; Oscar-Berman, 1990; Sullivan et al., 2000; Sullivan et al., 1997) and HIV infection (Fama et al., 2009; Gonzalez et al., 2008; Maki et al., 2009; Martin et al., 1993b; Martin et al., 2001; Rothlind et al., 2005). Chronic alcoholism is commonly marked by visuospatially-mediated and working memory impairments, whereas HIV infection is commonly marked by verbally-mediated and episodic memory impairments. These differential patterns of declarative memory impairment in chronic alcoholism and HIV infection likely reflect the neuropathology associated with these conditions: frontocerebellar dysfunction in chronic alcoholism (Sullivan et al., 2003) and frontostriatal dysfunction in HIV infection (Castelo et al., 2006), with limbic system compromise common to both conditions. Persistent cognitive deficits have been documented in both chronic alcoholism with long-term abstinence (e.g., Fein et al., 1990; Fein and Chang, 2006; Rosenbloom et al., 2008) and HIV infection treated with antiretroviral agents (e.g., Cysique and Brew, 2009). In particular, deficits in higher-order executive functions, components of memory, and visuomotor abilities have been documented even after long-term abstinence in alcoholics (Beatty et al., 1996; Brandt et al., 1983; Fein et al., 2006; Goldman et al., 1983), although selective cognitive and motor abilities (e.g., attention, working memory, psychomotor speed) can show some recovery. Further, evidence for disease overlap has been observed with documented compounded impairments in cognitive processes in alcoholism-HIV comorbidity (Fama et al., 2007; Fama et al., 2009; Rothlind et al., 2005). The majority of memory-related studies in chronic alcoholism and HIV infection has focused on component processes of declarative memory. Less is known about how these conditions and their comorbidity affect nondeclarative memory processes, which could be independently disrupted by neuropathology unique to each condition. Studies of procedural learning, many of which have used rotary pursuit testing to assess visuomotor speed and learning, have generally reported learning deficits in individuals with primary subcortical dysfunction (e.g., Huntington’s disease - (Gabrieli et al., 1997; Heindel et al., 1988); Parkinson’s disease - (Haaland et al., 1997)), whereas these processes are relatively intact in individuals with conditions primarily affecting cortical or medial temporal structures (e.g., Alzheimer’s disease - (Heindel et al., 1989); global amnesia - (Cermak and Butters, 1973; Cohen and Squire, 1980; Corkin, 1968; Tranel et al., 1994)). In addition to subcortical influences on visuomotor learning processes, damage to the cerebellum and associated neural networks is known to impair visuomotor learning, particularly in tasks requiring anticipatory movement (Ivry and Keele, 1989; Schugens et al., 1998). Martin and colleagues (Martin et al., 1993a) were the first to demonstrate procedural learning deficits in a subgroup of HIV infected subjects. Seven of their 29 HIV-infected subjects (24%) exhibited impaired motor speed and learning on a rotary pursuit task, and this impairment was not associated with CD4 counts. Later, Gonzalez and colleagues (Gonzalez et al., 2008) examined 48 HIV-infected individuals and 48 control subjects on a rotary pursuit task (speed set at 55 rpm for all subjects) and found that the HIV group was impaired compared with the control group on the initial testing session; yet, both groups demonstrated learning across trials. These authors concluded that deficits reported in previous studies on the rotary pursuit task in HIV infection may be due to impairments in complex motor functions and processing speed rather than to a deficit in procedural learning per se. Doyon and colleagues (Doyon et al., 2003) have hypothesized that learning a visuomotor task comprises three phases: 1) learning, 2) consolidation, and 3) retention. The early, fast learning stage that occurs initially after presentation of a task is hypothesized to be primarily dependent on intact cortico-cerebellar circuitry, whereas the later, retention stage is primarily dependent on intact cortico-striatal circuitry. The consolidation phase, the time between testing sessions, is dependent on limbic structures and surrounding circuitry. Grafton and colleagues (Grafton et al., 1994) using PET provided support for this hypothesis, reporting that initial acquisition of motor skills accompanied recruitment of cortical and cerebellar areas, whereas learning based on continued practice was associated with activity in the striatum. These findings suggest that cortico-cerebellar and cortico-striatal circuits make independent contributions to visuomotor learning tasks. Thus, individuals comorbid for chronic alcoholism and HIV infection may manifest both frontocerebellar and frontostriatal compromise and be dually affected, demonstrating greater impairment in visuoperceptual speed and procedural learning than individuals affected by only one condition. Visuomotor procedural processes are functionally and structurally multifaceted. Successful learning reflects intact motor, perceptual, memory, and executive functions (cf., Schmidtke et al., 2002). Dysfunction in any one of these component processes contributing to visuomotor learning can contribute to impairment, and processes involved during initial learning may differ from the component processes associated with consolidation and retention. Schmidtke and colleagues (Schmidtke et al., 2002) showed that visuospatial performance in patients with frontostriatal lesions (sum of scaled scores of Block Design and Object Assembly from WAIS-R) predicted initial performance on a rotary pursuit task, whereas verbal fluency scores predicted subsequent learning. The aims of the present study were (1) to examine visuomotor learning and retention on the rotary pursuit task in individuals with chronic alcoholism, HIV infection, and those comorbid for alcoholism and HIV infection compared with control subjects and (2) to investigate the mnemonic and nonmnemonic component processes underlying learning and retention performance in each clinical group. We tested the following hypotheses: (a) all groups would show visuomotor learning and retention across trials, although the comorbid group would demonstrate the greatest deficits of all the groups in motor and memory related processes; (b) the HIV-infected groups (HIV, ALC+HIV) would demonstrate slowed visuomotor speed compared with the control group; (c) although the single diagnosis groups (ALC, HIV) would not differ from each other on overall visuomotor learning scores, the HIV group would show better early learning than the ALC group (based on ALC-related presumed cerebellar compromise), whereas the ALC group would show better consolidation and retention compared to the HIV group (based on HIV-related presumed striatal compromise); and (d) visuomotor speed and learning in the three clinical groups would be associated with selective cognitive processes (e.g., psychomotor processing speed, memory, executive functions) rather than being associated with simple motor speed ability (e.g., finger movements).