Neural correlates of attention and working memory deficits in HIV patients

Chang, Linda; Speck, Oliver; Miller, Eric N.; Braun, Jochen; Jovicich, Jorge; Koch, Christof; Itti, Laurent; Ernst, Thomas

doi:10.1212/wnl.57.6.1001

Cited by 184 publications

(167 citation statements)

References 43 publications

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“…At baseline, HIV participants showed a reorganized neural network compared to SN participants even on the relatively simple 1‐back task, with greater activation in the medial and lateral frontal regions, but lesser activation in brainstem and bilateral cingulate gyri, which are consistent with previous studies of WM and sustained attention tasks in HIV participants 20, 22, 23, 41. Similarly, on the 2‐back task, the greater activation in bilateral medial frontal regions and the right precentral gyrus is also consistent with greater usage of the reserve attention network, or increased attentional modulation for this more‐difficult task in HIV patients 21, 24…”

Section: Discussionsupporting

confidence: 88%

“…On fMRI, both groups showed typical robust activation patterns during the 1‐back and 2‐back WM tasks20, 22 (Figs 4 and 5). On the 1‐back task, HIV participants showed greater activation than SN controls (FDR corrected, p < 0.0001) in frontal regions, with local maxima at the left cingulate gyrus (Brodmann's area [BA] 24), left medial frontal gyrus (BA 6), and right middle frontal gyrus (BA 9; Supplementary Table 1).…”

Section: Resultsmentioning

confidence: 93%

“…This is the first study to show improved (decreased) brain activation on BOLD‐fMRI, suggesting improved neural efficiency in HIV‐patients 1 month and further at 6 months after adaptive WMT. However, the decreased activation occurred in higher cortical regions in HIV patients, but primarily in subcortical regions in SN controls, attributed to normalization of the initially reorganized neural networks in patients with HIV‐associated brain injury 20, 21, 24. Furthermore, better overall WM performance and the greater improvement on brain activation in those with LMX 1A‐AA genotype likely reflect greater dopaminergic reserve.…”

Section: Discussionmentioning

confidence: 97%

“…(2) To assess the neural correlates of adaptive WMT, we performed blood‐oxygenated‐level–dependent (BOLD) functional magnetic resonance (MR) imaging (MRI) (fMRI) to evaluate changes in the neural network at 1 and 6 months after the training. Based on previous work, we expect HIV patients to show a baseline reorganized or adapted WM network, with lesser activation within the normal WM network, but greater activation in the reserve networks, compared to controls 20, 21, 22, 23, 24. After the adaptive WMT, improved efficiency in the neural networks would lead to decreased activation in the extent and magnitude of the BOLD signal in both groups.…”

mentioning

confidence: 98%

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Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

Chang

Løhaugen

Andres

et al. 2016

Annals of Neurology

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ObjectiveWe aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A‐rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls.MethodsA total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near‐transfer WM tests (Digit‐Span, Spatial‐Span), self‐reported executive functioning, and functional magnetic resonance images during 1‐back and 2‐back tasks were performed at baseline and each follow‐up visit, and LMX1A‐rs4657412 was genotyped in all participants.ResultsAlthough HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p < 0.0008) and nontrained WM tests after adaptive WMT (FDR corrected, p ≤ 0.001), but not after nonadaptive WMT (training by training type corrected, p = 0.01 to p = 0.05) 1 month later. HIV participants (especially LMX1A‐G carriers) also had poorer self‐reported executive functioning than SN, but both groups reported improvements after adaptive WMT (Global: training FDR corrected, p = 0.004), and only HIV participants improved after nonadaptive WMT. HIV participants also had greater frontal activation than SN at baseline, but brain activation decreased in both groups at 1 and 6 months after adaptive WMT (FDR corrected, p < 0.0001), with normalization of brain activation in HIV participants, especially the LMX1A‐AA carriers (LMX1A genotype by HIV status, cluster‐corrected‐p < 0.0001).InterpretationAdaptive WMT, but not nonadaptive WMT, improved WM performance in both SN and HIV participants, and the accompanied decreased or normalized brain activation suggest improved neural efficiency, especially in HIV‐LMX1A‐AA carriers who might have greater dopaminergic reserve. These findings suggest that adaptive WMT may be an effective adjunctive therapy for WM deficits in HIV participants. ANN NEUROL 2017;81:17–34

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 98%

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Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

Chang

Løhaugen

Andres

et al. 2016

Annals of Neurology

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“…Some of the earliest neuroimaging studies of HAND utilized MRS and found widespread evidence of aberrant metabolite levels suggesting severe inflammation and neural loss at all stages of infection [7]–[11]. Several fMRI studies have investigated neural activation during attention and working memory tasks in HIV-infected patients with and without cognitive impairment [12]–[16]. These studies have shown that HIV-infected patients exhibit greater activation and/or larger load-dependent increases in activation within the frontal and parietal cortices serving task performance [12]–[16].…”

Section: Introductionmentioning

confidence: 99%

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

et al. 2013

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ObjectiveShortly after infection, HIV enters the brain and causes widespread inflammation and neuronal damage, which ultimately leads to neuropsychological impairments. Despite a large body of neuroscience and imaging studies, the pathophysiology of these HIV-associated neurocognitive disorders (HAND) remains unresolved. Previous neuroimaging studies have shown greater activation in HIV-infected patients during strenuous tasks in frontal and parietal cortices, and less activation in the primary sensory cortices during rest and sensory stimulation.MethodsHigh-density magnetoencephalography (MEG) was utilized to evaluate the basic neurophysiology underlying attentive, visual processing in older HIV-infected adults and a matched non-infected control group. Unlike other neuroimaging methods, MEG is a direct measure of neural activity that is not tied to brain metabolism or hemodynamic responses. During MEG, participants fixated on a centrally-presented crosshair while intermittent visual stimulation appeared in their top-right visual-field quadrant. All MEG data was imaged in the time-frequency domain using beamforming.ResultsUninfected controls had increased neuronal synchronization in the 6–12 Hz range within the right dorsolateral prefrontal cortex, right frontal eye-fields, and the posterior cingulate. Conversely, HIV-infected patients exhibited decreased synchrony in these same neural regions, and the magnitude of these decreases was correlated with neuropsychological performance in several cortical association regions.ConclusionsMEG-based imaging holds potential as a noninvasive biomarker for HIV-related neuronal dysfunction, and may help identify patients who have or may develop HAND. Reduced synchronization of neural populations in the association cortices was strongly linked to cognitive dysfunction, and likely reflects the impact of HIV on neuronal and neuropsychological health.

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Adaptation of the attention network in human immunodeficiency virus brain injury

Chang

Tomasi

Yakupov

et al. 2004

Annals of Neurology

117

111

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Human immunodeficiency virus (HIV)-positive patients commonly have attention and concentration problems. However, it remains unclear how HIV infection affects the attention network. Therefore, blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) was performed in 36 subjects (18 HIV and 18 seronegative [SN] controls) during a set of visual attention tasks with increasing levels of attentional load. Compared with SN controls, HIV subjects showed similar task performance (accuracies and reaction times) but decreased activation in the normal visual attention network (dorsal parietal, bilateral prefrontal, and cerebellar regions) and increased activation in adjacent or contralateral brain regions. Cognitive performance (assessed with NPZ-8), CD4, and viral load all correlated with activated BOLD signals in brain regions that activated more in HIV subjects. Furthermore, HIV subjects activated more than SN controls in brain regions that showed load-dependent increase in activation (right prefrontal and right parietal regions) but less in regions that showed a saturation effect with increasing load. These findings suggest that HIV-associated brain injury leads to reduced efficiency in the normal attention network, thus requiring reorganization and increased usage of neural reserves to maintain performance during attention-requiring tasks. Exceeding the brain reserve capacity may lead to attention deficits and cognitive impairment in HIV patients.

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Neural correlates of attention and working memory deficits in HIV patients

Cited by 184 publications

References 43 publications

Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

Adaptive working memory training improved brain function in human immunodeficiency virus–seropositive patients

Abnormal MEG Oscillatory Activity during Visual Processing in the Prefrontal Cortices and Frontal Eye-Fields of the Aging HIV Brain

Adaptation of the attention network in human immunodeficiency virus brain injury

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