dysfunction of fronto-striatal circuits including associated parietal areas, the latter of which may account for observed deficits in visuospatial function. In addition to cognitive impairments, psychological dysfunction is also noted. For example, patients with HIV have higher rates of clinical depression and alexithymia, i.e., difficulty processing or recognizing one's own emotions. Patients also have more difficulty recognizing facial emotions. Without combination antiretroviral therapy, cognitive impairments increase with successive stages of HIV. HIV patients in early stages show mild difficulties in concentration and attention. In advanced cases of HIV-associated dementia, speech delay, motor dysfunction, and impaired thought and behavior are observed. Specifically, lower motor speeds were found to correlate with hypertrophy of the right putamen. The diagnosis of HIV-associated neurocognitive impairment is made using clinical criteria after considering and ruling out other possible causes. The severity of neurocognitive impairment is associated with nadir CD4, suggesting that earlier treatment to prevent immunosuppression due to HIV may help prevent HIV-associated neurocognitive disorders. Pathophysiology HIV-associated dementia (HAD) is not a true opportunistic infection; it is one of the few conditions caused directly by HIV itself. However, the cause of HAD can be difficult to discern because the central nervous system can be damaged by a number of other causes related to HIV infection: opportunistic infections AIDS-related lymphoma or metastasis of other AIDS-related cancers direct effects of HIV in the brain toxic effects of drug treatments malnutrition Many researchers believe that HIV damages the vital brain cells, neurons, indirectly. According to one theory, HIV either infects or activates cells that protect the brain, known as macrophages and microglia. These cells then produce toxins that can set off a series of reactions that instruct neurons to self-destruct. The infected macrophages and microglia also appear to produce additional factors such as chemokines and cytokines that can affect neurons as well as other brain cells known as astrocytes. The affected astrocytes, which normally nurture and protect neurons, also may now end up harming neurons. Astrocytes produce neurotoxic proteins such as Tat, Nef and Rev. Tat is secreted and induces reactivity in astrocytes through increased GFAP expression. HIV protein gp120 inhibits the stem cells in the brain from producing new nerve cells. In the neuronal cells, the HIV gp120 induces mitochondrial-death proteins like caspases, which may influence the upregulation of the death receptor Fas leading to apoptosis. Direct effects of HIV HIV enters the brain early on in the