White Matter Coupling Imbalance Marks Early HIV Neurocognitive Impairment

Even with effective viral suppression through modern antiretroviral regimens, HIV-associated neurocognitive disorders remain a prevalent comorbidity [1]. The earliest phase, asymptomatic neurocognitive impairment, often eludes detection in routine clinical practice because it lacks overt functional deficits and typically requires time-intensive neuropsychological batteries for diagnosis [2]. While subcortical gray matter atrophy was historically considered the primary driver of these deficits, contemporary research highlights the critical role of white matter microstructural damage, specifically demyelination and axonal loss [3, 4]. Advanced techniques like diffusion tensor imaging (a method that measures the directionality of water diffusion to assess fiber tract integrity) have consistently identified these structural changes even in patients with well-controlled viral loads [5]. A new study now examines how the spatial alignment of structural and functional signals within white matter might provide a more sensitive marker for neurodegeneration, bridging the gap between physical decay and physiological signaling.