Table 4.
Studies investigating imaging correlates of cognitive function in JME and AE.
| Reference | Design | Patients/Controls (n) | Patient Age (sd) | Age of epilepsy onset (sd) | Disease duration (sd) | AED regimen | Summary |
|---|---|---|---|---|---|---|---|
| JME | |||||||
| Swartz et al. (86) | C | 9/14 | 28.0 (4.0) | 9–20 | N/A | Polytherapy | FDG-PET− 1) Rest: ventral premotor, dorsolateral frontal, temporal, limbic and caudate hypometabolism in JME 2) Working Memory: dorsolateral frontal, premotor and basal frontal hypometabolism, fusiform and temporo-polar hypermetabolism |
| Savic et al. (138) | C | 26/10 | 30.6 (7.7) | 13.6 (3.0) | 17.2 (8.2) | Mixed | MR Spectroscopy—Reduced processing speed and cognitive flexibility scores in JME patients with lower frontal lobe N-Acetyl Aspartate concentration |
| McDonald et al. (139) | C | 10/14 | 27.9 (4.7) | N/A | N/A | N/A | FDG-PET—No frontal hypometabolism in JME. Bilateral orbito-frontal and premotor metabolism related to non-verbal fluency, bilateral frontal hypometabolism associated with mental flexibility |
| Pulsipher et al. (140) | C | 20/51 | 15.5 (2.8) | 14.5 (3.0) | 8.9 (3.7) (months) | Mixed | Structural MRI—Smaller thalamic volumes and increased frontal cerebrospinal fluid in JME. Thalamic volumes related to cognitive flexibility in the JME and control groups, frontal gray matter associated with cognitive flexibility and response inhibition in the JME group only |
| Roebling et al. (93) | C | 19/20 | 24.2 (9.9) | N/A | N/A | Mixed | Structural MRI and working memory fMRI—No gray matter volume differences between patients with JME and controls, and no intergroup activation differences during a verbal and a visuo-spatial working memory task |
| O'Muircheartaigh et al. (94) | C | 28/55 | 33.6 (10.1) | 14.4 (3.4) | 20.2 (10.3) | Mixed | Structural MRI—in JME, fractional anisotropy of anterior SMA positively correlated with naming performance, fractional anisotropy and gray matter volume of the posterior cingulate cortex negatively correlated with processing speed |
| Vollmar et al. (141) | C | 30/26 | 32.8 (9.9) | N/A | N/A | Mixed | Working memory fMRI−1) abnormal co-activation of motor cortex and SMA with high cognitive load, and 2) impaired deactivation of the default-mode network in JME |
| Kim et al. (95) | C | 25/30 | 25.3 (7.6) | 14.7 (3.1) | 10.6 (7.7) | Mixed | DTI—Impairment of processing speed, phonemic fluency, working memory, cognitive flexibility, and response inhibition in JME not correlated with fractional anisotropy or mean diffusivity abnormalities |
| O'Muircheartaigh et al. (129) | C | 28/27 | 34.1 (9.9) | 14.8 (2.7) | 8.7 (11.5) | Mixed | Language fMRI—Phonemic fluency scores associated with attenuation of thalamocortical connectivity during verbal fluency paradigm, which was defective in JME |
| Lin et al. (96) | C | 56/42 | 26.5 (9.0) | 12.5 (4.6) | 14.3 (10.0) | Mixed | Structural MRI—In JME, hippocampal volumes associated with performance on tests of semantic knowledge, phonemic fluency, verbal memory and learning |
| Wandschneider et al. (97) | C | 21/11 | 33.5 (22–64)** | N/A | N/A | Mixed | fMRI—Poor decision-making associated with bilateral dorsolateral frontal activation in JME, and with reduced DMN deactivation in controls. Performance in JME patients with ongoing seizures negatively correlated with dorsolateral frontal activation. Non-learners had stronger activation of pre-SMA, left dorsolateral frontal cortex, and right superior frontal gyrus than learners |
| Lin et al. (142) | L# | 19/57 | 14.9 (0.7) | 14.0 (0.7) | 8.4 (0.9) | Mixed | MRI—Lower longitudinal improvement in IQ, processing speed, and response inhibition scores in JME related to attenuation of the expected cortical thinning and surface area reduction in fronto-temporo-parietal association areas |
| Caeyenberghs et al. (143) | C | 35/35 | 26.8 (7.8) | 15.0 (3.5) | 15.2 (8.8) | Mixed | Structural MRI—Tractography-based connectivity between right precuneus and left postcentral gyrus positively correlated with VIQ, naming, abstract reasoning, and verbal memory. Connectivity between right hippocampus and right postcentral gyrus also associated with abstract reasoning. |
| Caciagli et al. (108) | C | 37/36 | 32.0 (14.0)*** | 15.0 (4.0)*** | 19.0 (16.0)*** | Mixed | Structural MRI—IQ and memory scores not associated with hippocampal malrotation in JME. Memory fMRI—Abnormal mesiotemporal and dorsolateral frontal activation in all JME patients during verbal memory, reorganized mesiotemporal activation for visual memory in JME with hippocampal malrotation only |
| AE | |||||||
| Caplan et al. (144) | C | 26/37 | 9.7 (2.1) | 6.9 (2.1) | 2.2 (2.3) | Mixed | Structural MRI—Gray matter volume loss in left orbital frontal gyrus and bilateral temporal lobes in CAE. Volume of these areas related to IQ in controls, not in patients. |
| Killory et al. (145) | C | 26/22 | 12.0 (4.0) | N/A | N/A | Mixed | EEG-fMRI—Decreased medial frontal fMRI activation associated with poorer continuous performance test results in CAE. Concomitant impaired connectivity within attentional networks in CAE compared to controls |
| Tosun et al. (114) | C | 24/28 | 9.2 (2.2) | 7.0 (2.0) | 2.3 (2.2) | Mixed | Structural MRI (SBM) 1) Sulcal depth: PIQ and VIQ less associated with medial/superior frontal, superior temporal, and occipito-parietal sulcal depth in CAE than controls, and more associated with middle frontal sulcal depth in CAE than controls 2) Cortical thickness: frontal and temporal thickness less associated with PIQ and VIQ in CAE than controls, while orbito-frontal thickness is more associated with PIQ and VIQ in CAE |
| Lin et al. (146) | C | 21/27 | 9.6 (2.1) | 7.0 (2.1) | 2.6 (2.5) | Mixed | Structural MRI—in CAE, no association between thalamic volumes and cognitive measures (IQ, SLQ), but negative correlation detected between left thalamic volume and scores on a social problem assessment scale. |
| Guo et al. (147) | C | 39/ no controls | 9.9 (3.1) | N/A | 3.0 (2.5) | Medication withheld 48h prior to scanning | EEG-fMRI during tasks—Absence seizures with behavioral impairment during finger tapping and attention tasks associated with more marked fMRI signal increases in default-mode, fronto-parietal and thalamic-/sensory-motor network than seizures with no impairment in task performance. |
Studies are listed in chronological order. Unless specified otherwise, age, age of epilepsy onset and disease duration are reported as mean values in years, or as ranges, if provided in such format by the original reference.
**
Median (range).
***
Median (interquartile range).
#
Demographics are provided for the sample at baseline. C, Cross-sectional design; CAE, Childhood Absence Epilepsy; DMN, Default Mode Network; DTI, Diffusion Tensor Imaging; (f)MRI, (Functional) Magnetic Resonance Imaging; IQ, Intelligence Quotient; JME, Juvenile Myoclonic Epilepsy; L, Longitudinal Design; PIQ, Performance Intelligence Quotient; SBM, Surface Based Morphometry; SLQ, Spoken Language Quotient; SMA, Supplementary Motor Area; VIQ, Verbal Intelligence Quotient. Mixed AED status is given for studies where AED use was not restricted to a single regimen (i.e., monotherapy, polytherapy, or drug-naïve).