Functional reorganisation and recovery following cortical lesions: A preliminary study in macaque monkeys

Abstract

Damage following traumatic brain injury or stroke can often extend beyond the boundaries of the initial insult and can lead to maladaptive cortical reorganisation. On the other hand, beneficial cortical reorganisation leading to recovery of function can also occur. We used resting state FMRI to investigate how cortical networks in the macaque brain change across time in response to lesions to the prefrontal cortex, and how this reorganisation correlated with changes in behavioural performance in cognitive tasks. After prelesion testing and scanning, two monkeys received a lesion to regions surrounding the left principal sulcus followed by periodic testing and scanning. Later, the animals received another lesion to the opposite hemisphere and additional testing and scanning. Following the first lesion, we observed both a behavioural impairment and decrease in functional connectivity, predominantly in frontal-frontal networks. Approximately 8 weeks later, performance and connectivity patterns both improved. Following the second lesion, we observed a further behavioural deficit and decrease in connectivity that showed little recovery. We discuss how different mechanisms including alternate behavioural strategies and reorganisation of specific prefrontal networks may have led to improvements in behaviour. Further work will be needed to confirm these mechanisms.

Keywords: FMRI; Neuropsychology; Plasticity; Prefrontal cortex; Recovery of function; Resting state covariance.

Fig. 1

Assessing behavioural impairments and cortical reorganisation following lesions to the principal sulcus. A) Behavioural testing took place with the monkeys unrestrained in transport boxes, facing a touchscreen. In the ‘match-to-location’ task (left), the monkey was required to touch a cue that appeared in a random location on the touchscreen. The cue then disappeared and after a distractor (central blue square) and variable delay, three stimuli identical to the cue appeared in three different locations. The three locations included the sample location from the current trial, the cued location from a previous trial, and a third random location. The monkey was required to touch the location of the cue on the current trial to receive a food pellet reward. In the ‘match-to-object’ task (right), the monkey was once again required to touch a cue that appeared in a random location on the touchscreen. After a variable delay, two different stimuli appeared in random locations: the sample stimulus and a distracter stimulus. The monkey was required to touch the sample stimulus to receive a food pellet reward. B) Time course of our longitudinal experiment. We collected behavioural (green boxes) and MR (blue boxes) data at periodic intervals (approximately every 3–4 weeks) both before and after the PS lesions (red boxes). These sessions were grouped in pre- and post-lesion periods (indicated by square outlines). In the case of first prelesion period (Prelesion 1), the two scanning/behavioural sessions were separated by approximately 6 months. After the first lesion, scanning/behavioural data were collected every 3–4 weeks. In the case of the second prelesion period (Prelesion 2), we collected behavioural data at two timepoints prior to the lesion, separated by about 3–4 weeks. However, we were unable to collect MR data immediately prior to the second lesion, and so we used the MR data from the “Post-Lesion 1-Late” period as the prelesion data for the second lesion. C) Location and anatomical connectivity for regions in our network of interest. Connectivity based on Yeterian et al. (2012) and Saleem et al. (2014). TE: area TE; PMd: dorsal premotor area; PMv: ventral premotor area; LIP: lateral intraparietal area; 7b, 8, 9, 46: areas 7b, 8, 9, 46; VLPFC: ventrolateral prefrontal cortex; preSMA: pre-supplementary motor area; PS: principal sulcus.

Fig. 2

Structural MRIs showing location of first and second lesions in monkey 1 and 2. Coronal slices showing lesion to principal sulcus. Anatomical distances shown relative to the interaural axis.

Fig. 3

Behavioural performance of both monkeys in the match-to-location (solid lines) and match-to-object (dashed lines) tasks. Data are plotted as mean+/-SEM. A) Following a lesion to the left principal sulcus, both monkeys showed a significant drop in performance in both tasks in the testing sessions conducted within 8 weeks of the lesion. In the behavioural testing sessions beginning about 8 weeks post-lesion, behaviour showed overall improvement. B) After a second lesion to the right principal sulcus, there was again behavioural decline followed by partial improvement. (*p < 0.05).

Fig. 4

Connectivity within frontal lobes impaired following lesion to regions near the left principal sulcus. A) Average correlation for all frontal-frontal, frontal-parietal, and frontal-temporal connections in the pre-lesion, early-post-lesion (4–8 weeks post lesion) and late post-lesion (8–16 weeks) periods. B) Schematic representations of changes to connectivity in the early post-lesion (left) and late post-lesion (right) periods, relative to the pre-lesion period. Significant increases in functional connection strength (correlation) shown in red; decreases in blue. Filled red circles indicate lesioned hemispheres.

Fig. 5

Connectivity within frontal lobes impaired following lesion to regions near the right principal sulcus. A) Average correlation for all frontal-frontal, frontal-parietal, and frontal-temporal connections in the pre-lesion, early-post-lesion (4–8 weeks post lesion) and late post-lesion (8–16 weeks) periods. B) Schematic representations of changes to connectivity in the early post-lesion (left) and late post-lesion (right) periods, relative to the pre-lesion period. Significant increases in functional connection strength (correlation) shown in red; decreases in blue. Filled red circles indicate lesioned hemispheres.