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Postoperative haptic training facilitates the retrieval of visual-based memories after visual cortex lesions in rats
Physiology & Behavior 78 (2003) 601 – 609
Postoperative haptic training facilitates the retrieval of visual-based memories after visual cortex lesions in rats M. Claire Cartford1, Annette J. Beaver, Katrina A. Wagner, Eugene R. Delay* Department of Psychology, Regis University, 3333 Regis Boulevard, Denver, CO 80221, USA Received 30 April 2002; received in revised form 9 December 2002; accepted 28 January 2003
Abstract Two experiments examined the effects of postoperative haptic discrimination training on the relearning of a maze visual discrimination in rats with visual cortex lesions. In the first experiment, rats learned a visual intensity discrimination prior to ablation of the lateral Oc2L cortex. Lesion rats were exposed to either a rough/smooth haptic discrimination training condition, a random training condition, or a notraining condition prior to relearning the visual task. Lesion rats relearned the visual task faster after haptic training than after other postoperative experiences. The second experiment replicated these procedures but with rats in which most of the visual cortex was removed. The lesion-induced relearning deficits in the second experiment were similar to the deficits seen for the smaller Oc2L lesions in the first experiment, supporting the hypothesis that the lateral visual cortex is critical for intensity discrimination. Haptic training also reduced these deficits, but the magnitude of this effect was related to the characteristics of the haptic cue. Postoperative training with haptic cues can produce specific and nonspecific information transfer from the intact somatosensory system to the damaged visual system that can facilitate the visual relearning. Possible implications for neuropsychological rehabilitation are also discussed. D 2003 Elsevier Science Inc. All rights reserved. Keywords: Visual discrimination; Haptic discrimination; Cross-modal transfer; Reference memory
1. Introduction In recent years, our understanding of the interrelationships between sensory modalities, cognitive function, and the functional organization of brain structures underlying these relationships have been advanced with modern imaging techniques and the study of brain-injured patients. For instance, a recent positron emission tomographic study revealed modality-specific and multimodal regions of the human brain active during tactile, visual, and tactile –visual discrimination tasks [1,2]. Others have identified attentional processes that can link common elements of different modalities during cognitive processing [3]. Awareness of the potential clinical relevancy of these relationships has been increased by studies of functions such as bimodal extinction in patients with cortical injuries (cf. Refs. [4,5]) and by the development of neurorehabilitation programs * Corresponding author. Tel.: +1-303-458-4976; fax: +1-303-9645527. E-mail address: [email protected] (E.R. Delay). 1 Present address: Center for Aging and Brain Repair, University of South Florida, Tampa, FL, USA.
that use sensory cues in more than one sensory modality. In these treatment programs, it is generally assumed that cues presented to undamaged sensory modalities support or reinforce the cues processed by the less efficient, damaged sensory modality. However, the success of these treatment programs has been moderate [6 – 8] or equivocal [9,10]. Research examining the effects of cross-modality transfer (CMT) of learning in brain-damaged rats may provide some insight into the efficiency and the generalization of multisensory rehabilitation approaches. CMT of discrimination learning involves the transfer of information from a task using cues in one sensory modality to a similar task subsequently learned using cues in a second modality [11]. For example, a subject learns first to discriminate between two visual stimuli of different intensities, and then learns to discriminate between two stimuli of different intensities in a second modality. CMT is seen if the rate of learning of the second discrimination is faster for this subject than for a control subject who did not receive experience with the first modality or who received experience with different but comparable stimuli. CMT can occur when the stimuli of the two modalities share common attributes such as temporal patterns or duration, location, or relative intensity [12 – 14].
0031-9384/03/$ – see front matter D 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0031-9384(03)00045-3
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The capacity for transfer between visual and auditory modalities in rats has been established with a variety of discrimination tasks [14 – 17]. Importantly, this capacity is at least partially accessible to brain-damaged rats [18] and is capable of aiding recovery of behavior following cortical injury. For example, in one study [19], rats learned an avoidance response when a visual intensity cue preceded shock. After ablation of the visual cortex, these rats were given similar avoidance training with an auditory intensity cue the day before relearning the visual discrimination. Surprisingly, these rats relearned the visual discrimination in significantly fewer trials than other lesion rats given equivalent training with the preoperative visual discrimination. More recent studies have reported similar findings for several behavioral tasks including recovery of temporal discriminations [20] and auditory discrimination behavior after auditory cortex lesions [21]. Moreover, postinjury auditory training not only substantially reduced large behavioral deficits seen with a visual serial reversal learning task, but also showed better generalization than training with the damaged visual system [22]. These findings suggest that postinjury CMT training has the potential to reduce a variety of neuropsychological deficits. To date, however, all of these studies used only auditory and visual stimuli within an active shock-avoidance paradigm. On the other hand, most of the research in CMT with brain-injured humans and monkeys has focused on interactions between the visual and somatosensory modalities (for a review, see Ref. [11]). Although several studies were unable to detect significant alterations in somato-visual CMT following cortical lesions (e.g., Refs. [26,27]), others observed somato-visual CMT but also found impaired CMT after either large cortical lesions or lesions involving the parietal cortex [28 –31]. Thus, the area of the cortex that is damaged might play a significant role in whether postoperative CMT training will be of benefit depending on the sensory modalities involved. Understanding the areas of the cortex that contribute to mnemonic processes that are accessible by multiple sensory modalities is important for developing successful CMT strategies for brain-injured patients. Studies of somato-visual CMT with rats are lacking, but if one considers bimodal conditioning studies, this capacity may be limited in rats with damage to certain areas of the cortex. For instance, lesions in the anterior region of Oc2M of the extrastriatal cortex blocked conditional learning with bimodal visual and somatosensory stimuli [32] and, after large posterior lesions, postoperative compound conditioning with haptic and intensity cues interfered with the relearning of a preoperatively acquired visual intensity discrimination [23]. These findings suggest that posterior cortical lesions, particularly if the anteromedial extrastriatal cortex is involved, may impair somatovisual integration and thus might limit the effectiveness of somatosensory CMT as a ‘‘rehabilitation therapy.’’ Our goal was to use postinjury CMT training to examine a
possible therapeutic role for somato-visual interrelationships in a rat model. Two issues were addressed in this study. The first questioned whether postoperative somatosensory training can influence recovery of visual intensity discrimination after visual cortex lesions that spare most of the anteromedial extrastriatal cortex. This experiment showed that postoperative haptic training reduced visual relearning deficits when lesions were limited to the lateral visual cortex. Because of these findings, a second experiment was conducted to determine whether large visual cortex lesions that included the anteromedial extrastriatal cortex, a multisensory region with somato-visual functions [32 –34], would block the effects of somatosensory CMT training. This experiment showed that postoperative haptic training was still effective in facilitating visual relearning but was much more dependent upon the characteristics of the haptic cue. Since the design of the two experiments were essentially the same, they are presented together.
2. Materials and methods 2.1. Subjects The subjects for the two experiments were 80 male, naive Sprague – Dawley albino rats which, by the first training session, were between 90 and 120 days old and weighed between 320 and 420 g. They were housed singly in their home cages with food available ad libitum. All rats were trained during the light portion of the 12:12 LD cycle. The rats were maintained on a 23-h water-deprivation cycle and were handled for 5 – 10 min each day for at least six consecutive days prior to the first training session. 2.2. Apparatus All rats were trained in a two-arm maze described previously [35]. The maze, painted black throughout, had a start box connected to a 25 25-cm choice area which, in turn, was connected to two adjacent arms 10 50 cm long, each ending with a goal area (see Fig. 1). The floors of the start box and goal areas were stationary, but either of two removable floors could be positioned under the choice area and the maze arms. One floor, designed to present visual stimuli, was made of two sheets of transparent Plexiglas hinged on one side. The floor was divided into two halves by placing black and white stimuli, each extending the length of the choice area and one of the maze arms, between the Plexiglas sheets. For the white stimulus, white translucent paper was illuminated from beneath the floor by rows of 40-W Softwhite incandescent lights. The intensity of these lights, controlled with a dimmer switch, was 45 lx (Calcu-Light light meter, Quantum Instruments) at 0.5 cm above this half of the floor. For the black stimulus, black nontranslucent paper was placed over the other half of the
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Fig. 1. The two-choice maze with the stimulus floor (with visual stimuli) removed from beneath the maze. A portion of the light array below the floor of the maze can be seen in the cutaway.
floor. Light intensity of this side, measured as reflected light 0.5 cm above the surface of the floor, were between 0.67 lx at 1 cm from the border of the white half of the floor and less than 0.033 lx at 1 cm from the outer wall. The second removable floor, made to present the haptic stimuli, was also divided lengthwise into halves by rough and smooth stimuli mounted to the top of brown pressboard. The haptic stimuli were made from K-lux Clear Prismatic (PTC-25) fluorescent light cover paneling that was smooth on one side and had a repeating pattern of peaks and depressions on the other side (see Fig. 2). The basic pattern was a square measuring 4.6 mm on a side. The highest points of the pattern, located at each corner, were 1.0 mm above the center and lowest point of the pattern. A water well was located on the floor of the goal area of each arm. A fan generated 50 ± 2 dB during all training sessions.
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could cumulate over two sessions. All trials were counted toward criterion. A random sequence for locating the S+ and S during each trial was determined prior to each training session. To prevent the development of a side preference, the S+ could not be located on the same side for more than three consecutive trials, unless the procedure for an erroneous response was used. The time interval between trials ranged from 30 to 60 s. The training session for each rat lasted about 20 min, and then the rat was given access to a water bottle in the home cage for 40 min. Surgery was performed 24 h after the rat reached the criterion. Each rat was given atropine sulfate (0.15 cc, 10 mg/cc ip) to minimize salivation during surgery and then was anesthetized with sodium pentobarbital (50 mg/kg ip). Sham-operated rats were closed after opening the cranium. For rats in the lesion groups, the cranium was removed from the area immediately over the appropriate cortical region, the meninges were opened, and the cortical tissue was removed bilaterally by suction. After the incision was sutured, the rat was given Crystiben (0.1 cc, 300,000 units/cc im) to prevent infection and then was monitored for any postoperative complications. After surgery, rats were given 6 days of recovery before returning to the 23-h water-deprivation schedule. On the eighth day after surgery, eight rats in each experiment were assigned to one of five groups. One group of rats, hereafter identified as the intact group, was comprised of the shamoperated (n = 4) and normal control rats (n = 4). This group and a group of lesion rats were assigned to a no-training condition in which the rats remained in the home cage until the relearning procedures. One group of lesion rats was assigned to each of two haptic training conditions; one group was trained with the smooth surface as the S+, and
2.3. Procedure Each rat was allowed to explore the maze for at least 10 min on a clear acrylic floor without stimuli or reinforcers for 2 days. This was followed by a day of magazine training and 2 days of alternation training before the start of discrimination training. During discrimination training, a trial began when the door of the start box was raised and the rat entered the choice area. The water well in each maze arm was hidden behind a stimulus door that matched the floor. If the rat advanced halfway down the S+ arm, the goal door was removed to give the rat access to 0.15 ml of a 10% sucrose solution (w/v) reinforcer. To ensure that the rat remained in the maze arm for 10 s, a door was inserted at the entrance of the arm. If the rat entered the S arm, the goal door was not removed, the rat had to remain in the arm for a period of 30 s, and the S+ and S stimuli remained on the same side of the maze during the next trial. During preoperative training, half of the rats were trained with the white stimulus as the S+ and half were trained with the black stimulus as the S+ until they reached a criterion of 18 correct responses out of 20 (18/20) consecutive trials. Each session consisted of 20 trials, and criterion responses
Fig. 2. The repetitive pattern of the acrylic material that served as the rough haptic stimulus. The upper portion of the figure is an enlargement of four squares of the pattern. Fundamentally, each square was a concave surface with a peak in each corner. The peaks, 4.6 mm apart (A), were connected via a curvilinear ridge. The bottom of the ridge (B) was 0.8 mm below the peaks, and the center of the square (C) was 1.0 mm below the peaks. The opposite side of the material (D) was a relatively uniform surface that was used for the smooth haptic stimulus.
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the second group was trained with the rough surface as the S+. During haptic training, the lights beneath the maze were turned off and a red light located above the apparatus provided 6 lx of reflected light for the experimenter. In previous research, intact rats did not respond to visual stimuli under these conditions [35]. To determine whether exposure to cues, habituation to the apparatus and training procedures, or other nondiscrimination variables might have an effect during transfer training, a fifth group of lesion rats was given random haptic training. Random haptic training was identical to standard discrimination training except that the locations of the stimuli and the reinforcer were varied independently of each other. The haptic stimuli were randomly assigned to each arm of the maze and could be assigned to the same arms for as many as five consecutive trials. The location of the reinforcer was also randomized but could not occur in the same arm for more than three consecutive trials. If the rat entered the maze arm without the reinforcer, the rat was forced to stay in that arm for 30 s. In addition, the reinforcer was automatically located in the same arm on the next trial, but the haptic stimuli were free to vary according to the preassigned random sequence. Presentation order of the stimuli was checked to make sure that no more than chance pairings of the reinforcer and either stimulus occurred on a given training day. Each group was counterbalanced so that half of the rats were trained with the white S+ and half were trained with the black S+ during the preoperative session. Rats in the two haptic conditions and in the random training conditions were given 20 trials each day for 2 days. Ten days after surgery, each rat began retraining with the preoperative visual stimuli and was given 20 trials per day until it reached the 18/20 criterion. After each lesion rat reached the criterion for relearning, it was given an overdose of Nembutal, perfused with saline and then 10% formal saline, and the brain tissue was removed. Two independent observers mapped the extent of each lesion and quantified the area of each lesion with a grid overlay. Any discrepancies between the two maps were resolved before the tissue was frozen, sectioned at 20 um, and every 10th section stained with fast blue and cresyl violet for microscopic examination.
3. Results 3.1. Histological results 3.1.1. Experiment 1 The largest and smallest lesions of the lateral visual cortex are shown in Fig. 3. The following assessments of the lesions are based on Zilles and Wree’s [36] descriptions of the posterior cortical areas of the rat. These lesions included nearly all of the lateral aspects of Oc2L in every rat. The medial edge of the lesion infringed slightly into Oc1B and spared the anteromedial portion of Oc2L immediately rostral to Oc1. The anterior extent of the lesion was
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Fig. 3. The largest (stipple) and smallest (hatch) lesions of the lateral visual cortex in Experiment 1.
the most variable aspect of the lesions but invaded the posterior region of Par1 in every instance. In every case, the ventrolateral boundary of these lesions included the rostral areas of Te2 and Te3 adjacent to Oc2L and most encroached into the rostral region of Te1. These lesions also included some portion of the posterior perirhinal cortex (PRh), and a few extended into the posterior entorhinal area (Ent). Within these boundaries, the lesions extended into, but not through, the underlying radiations, and no damage to underlying subcortical structures was detected. Degeneration was detected in the dorsal lateral geniculate nucleus and the lateral posterior nucleus of the thalamus. Analysis of the areal measurements of the lateral lesions indicated that, on average, 5% of the tissue along the lateral and ventral edges of Oc2L was spared. Grid counts indicated that, on average, 15% of the anteromedial Oc2L was
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spared. Analysis of variance (ANOVA) did not find any group difference in estimated lesion size or in the amount of tissue spared [ F’s < 1.0]. 3.1.2. Experiment 2 The largest and smallest cortical lesions of the second experiment can be seen in Fig. 4. The lateral and posterior boundaries of these lesions were essentially the same as those described for Experiment 1. In addition, every lesion encompassed all of the anteromedial portions of Oc2L and all of Oc1 and Oc2M. The medial edge of these lesions invaded the lateral agranular retrosplenial cortex (RSA). The anterior portion of these lesions extended into the posterior area of the frontal areas Fr1 and Fr2, the primary somatosensory cortex (Par1), and included up to half of the hindlimb (HL) area. No lesion, however, extended into the
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forelimb area (FL). All lesions extended into, but not through, the underlying radiations. No damage to the underlying subcortical structures was detected. Degeneration was seen in the dorsal and ventral lateral geniculate, lateral posterior, and lateral dorsal thalamic nuclei. Areal measurements of the full lesions showed that less than 1% of the Oc1 and Oc2 areas were spared. ANOVA procedures did not detect any group differences in estimated lesion size or in the amount of tissue spared [ F’s < 1.0]. 3.2. Behavioral results In both experiments, the preoperative learning and postoperative relearning scores, representing the number of trials to criterion, were adjusted before analysis by subtracting 20, the learning criterion. Then the data for each experiment were subjected to ANOVA procedures and to post hoc and simple-effects tests, as needed. 3.2.1. Experiment 1 The analysis of the data for the rats with lesions of Oc2L revealed significant effects of pre- and postoperative visual discrimination sessions [ F(1,30) = 18.86, P < .001], postoperative haptic training conditions [ F(4,30) = 10.29, P < .001], and the interaction between these two variables [ F(4,30) = 18.96, P < .001; see Fig. 5]. One-way ANOVA indicated that trials to criterion for the five groups did not differ during the preoperative session [ F < 1.0] but differed significantly during the relearning session [ F(4,35) = 35.00, P < .001]. Simple-effects tests indicated that the random training and the notraining lesion groups required significantly more trials to reach criterion during the relearning session than during preoperative learning, whereas intact no-training and the two haptic discrimination groups required significantly fewer trials (all P’s < .025 or smaller). Newman– Keuls comparisons ( P < .05) of the relearning data showed that lesion groups in the random training and the no-training conditions took significantly more trials to reach criterion than the other three groups and that the scores of the rats given training with the smooth S+ were significantly higher than the scores of the rats trained with the rough S+. No analysis found any differences between light and dark S+. Finally, the scores of the intact group were significantly smaller than all other groups.
Fig. 4. The largest (stipple) and smallest (hatch) lesions of the visual cortex in Experiment 2.
3.2.2. Experiment 2 The ANOVA for the preoperative and postoperative visual discrimination data of the groups with large cortical lesions found significant main effects for postoperative haptic training conditions [ F(4,30) = 13.05, P < .001], sessions [ F(1,30) = 15.24, P < .001], and interactive effects between these two variables [ F(4,30) = 15.20, P < .001; see Fig. 6]. Separate analyses of scores for the pre- and postoperative sessions did not detect group differences in preoperative learning [ F < 1.0], but did for the scores of the second session [ F(4,35) = 20.09, P < .001]. Simple-effects
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relearned their visual discrimination in significantly fewer trials than the dark S+ group ( P < .001; see Fig. 6).
Fig. 5. The mean (S.E.M.) trials to criterion, less the criterion trials, for preoperative learning and postoperative relearning of the intact and lesion no-training groups and the random, smooth, and rough S+ haptic groups with lateral cortex lesions (Experiment 1).
tests ( P < .01) comparing the scores for the pre- and postoperative visual discrimination sessions showed that the postoperative trials to criterion scores of the intact control group and the two haptic lesion groups were significantly lower than their respective preoperative scores, whereas the postoperative scores of the random training and the notraining lesion groups were significantly higher than their preoperative scores. Newman –Keuls comparisons ( P < .05) showed that the intact control rats and the two groups of rats given haptic training had significantly better scores during the relearning session than the no-training and the random training lesion groups. Also, the intact rats had significantly lower scores than rats given postoperative training with the rough S+. In addition, a t test indicated that the light S+ group given postoperative training with the rough S+
Fig. 6. The mean (S.E.M.) trials to criterion, less the criterion trials, for preoperative learning and postoperative relearning of the rats conditioned with the light and dark S+ cues for each training group with large visual cortex lesions (Experiment 2). Training groups included the intact and lesion no-training groups and the random, smooth, and rough S+ haptic groups.
3.2.3. Comparisons across experiments The results of the individual experiments suggested that the effects of haptic training depended upon the nature of the visual S+ and the lesion. To test this, the scores of the rats trained with the smooth and the rough S+ in each experiment were compared. Although the design and execution of the two experiments were assumed to be equivalent, analysis of the preoperative learning scores indicated rats in the first experiment learned the visual discrimination in significantly fewer trials (mean = 24.00, S.E.M. = ± 2.35) than rats in the second experiment (mean = 31.00, S.E.M. = ± 1.22) [ F(1,24) = 7.43, P < .025]. Consequently, the data of each rat were normalized by dividing the relearning score by the preoperative learning score. This procedure generates a proportional score which, if less than 1.0, indicates retention of the task during relearning [19 –21,24]. An ANOVA of these scores revealed a significant three-way interaction between training conditions, the intensity of the visual cue, and the two lesions [ F(1,24) = 11.92, P < .001]. Newman– Keuls tests indicated that rats with the large lesions trained with the dark S+ and with the rough S+ during experimental training, required significantly more trials to relearn the visual discrimination than all other groups. Of the remaining groups, rats with lateral lesions trained with the light S+ and given postoperative training with either haptic S+ relearned the task in significantly more trials than the rats in the other conditions (see Fig. 7). Thus, the effects of postoperative haptic training conditions on relearning were dependent upon all three variables. Finally, neither the size of the lesion nor the amount of the target area was not correlated with the proportional scores (all r’s < .20).
Fig. 7. Mean (S.E.M.) proportional scores (relearning scores/preoperative learning scores) for rats with lateral visual cortex lesions (Experiment 1) and large lesions (Experiment 2) that were given smooth and rough haptic S+ training the day before relearning began.
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3.2.4. Experimental training Reinforced responses during experimental training were analyzed to examine the effects of lesion size (2), visual S+ (2), and haptic training condition (3). This ANOVA found a significant effect of training condition on reinforced responding [ F(2,36) = 12.28, P < .001]. Post hoc comparisons showed the groups given random training emitted significantly fewer reinforced responses (mean = 13.17, S.E.M. = 0.81) than those emitted by the rats given haptic training with either smooth (mean = 20.63, S.E.M. = 1.10) or rough S+ (mean = 19.44, S.E.M. = 1.17). In addition, the level of learning reached during haptic training was examined by determining the highest number of reinforced responses in 20 consecutive trials reached by the rats in both experiments. The analysis of these data indicated that haptic training condition was the only variable to significantly alter the level of learning with haptic cues [ F(2,21) = 4.43, P < .01]. Rats trained with the smooth and rough S+ reached significantly higher criteria of learning (smooth: mean = 11.94, S.E.M. = 0.61; rough: mean = 12.01, S.E.M = 0.65) than the rats in the random training condition (mean = 8.39, S.E.M. = 0.39). In summary, both lesions produced similar deficits during postoperative relearning. Random training procedures did not significantly alter the relearning deficit induced by either lesion. In contrast, training with either the rough or smooth S+ reduced relearning deficits, although not necessarily in an equivalent manner for the two visual intensity cues. After lesions of Oc2L, training with the rough S+ reduced the relearning deficit more than training with the smooth S+ with either visual cue. However, the rough S+ was much less effective at reducing the lesion deficit for rats with the large lesions trained with the dark S+ compared to all other conditions.
4. Discussion In these experiments, we sought to use a visual intensity discrimination learning model in the rat to examine potential effects of CMT between visual and somatosensory systems. The visual discrimination in this study differs somewhat from the two-choice maze discrimination tasks typically used in that the discriminative stimuli were located on the floor of the maze rather than as part of a vertically oriented display of either doors at or near the entrance of the maze arms or lights located somewhere within the arm. Replicating previous observations [35], the intact rats in this study readily learned and relearned this discrimination. Relearning deficits after lesions of the lateral visual cortex and after the larger, more complete lesion of the visual cortex, were comparable; that is, after either lesion relearning scores averaged approximately 50% higher than preoperative scores. The magnitude of the relearning deficits for these two lesions are relatively similar to each other even though the full lesions were much larger than the lateral lesions,
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ruling out explanations such as mass action. These findings agree with previous reports [37] and support the notion that the lateral area of Oc2L, an area particularly important for spatial contrast sensitivity [38], is the area of the rat’s visual cortex most involved in the retention of intensity discrimination within a maze task [37,39]. Haptic discrimination training reduced relearning deficits after either lateral or large visual cortex lesions. These findings are in agreement with earlier studies in which postoperative CMT training with an intact sensory modality reduced lesion deficits in retention and reversal learning of visual or auditory shock-avoidance tasks [19 – 22,24]. The positive effects of haptic training apparently are not the results of additional handling, habituation to the test apparatus, or exposure to testing procedures since relearning of the lesion rats in the random haptic training condition did not differ from the lesion rats in the no-training condition. Rather, training with either the smooth or rough S+ may have involved ‘‘multimodal’’ [12] or ‘‘amodal’’ [13,40,41] processes responsible for much of the beneficial effects of postoperative CMT training. A key characteristic of CMT, one that differentiates CMT from bimodal compound conditioning or conditional discrimination, is the temporal separation between the cues of the two modalities. In CMT, the temporal separation between training sessions allows the brain-injured rat to develop a reference memory or schema with the intact modality without biasing the rat away from using the damaged sensory system as it does during bimodal compound conditioning when cues are simultaneous and redundant [23,24]. Thus, during relearning, the lesion rat can draw on the schema as a functional compensatory mechanism to help retrieve preoperative memories of the visual discrimination task with the damaged neurological system [24,25]. The beneficial effects of haptic training on visual relearning seen in this study extend this notion to postoperative training with somatosensory cues in rats with lesions of the visual cortex. Although the positive effects of haptic CMT were expected after the lateral visual cortex lesions, the effects of haptic training on visual relearning following the large lesions were surprising. After the removal of the lateral visual cortex, cortical tissue between the somatosensory and the primary visual cortex remained intact and presumably could serve as the neurological basis for multimodal integration and transfer of learning between the somatosensory and the visual modalities. Others have found that unilateral damage to the posterior parietal area results in contralateral multimodal neglect [42,43]. Bilateral damage to the anterior portion of Oc2M disrupts bimodal somato-visual conditional discrimination ability [32] and lesions of the posterior parietal cortex blocks visual –auditory transfer when tasks involve spatial relationships [44]. Additionally, lesions of the posterior parietal region in rats impaired retention, but not acquisition, of an intensity discrimination (described as Areas 7, 39, and caudal 2 [37]). Collectively, these findings suggest that the
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cortex between the visual and somatosensory cortices, although probably not directly crucial to performing a visual intensity discrimination [37], is functionally important as a multimodal sensory association area [45]. While the results of the first experiment can be explained by this hypothesis, the results of the second experiment cannot, since the large lesions were deliberately extended into nearly all of the extrastriatal cortices, the posterior parietal cortex, and the striate cortex. Spared tissue surrounding the lesion, other cortical or subcortical structures of the visual system receiving multisensory input such as the visual region of the temporal cortex [33,34,46] or the superior colliculus [25], or other multimodal structures, may have been responsible for the effects of the postoperative haptic training on visual relearning in this study. A number of areas of the brain have been identified where CMT occurs but many of these multimodal structures such as the amygdala are involved in CMT only if they are closely related anatomically and functionally to the cognitive functions essential for the behavior. The CMT effects in this study may be functionally related to cross-modal memory functions associated with the frontal cortex [47 – 49], the amygdala [50,51], or the hippocampus [51 – 54]. It is also conceivable that more than one area might combine cross-modal functions such as the working memory functions of the frontal cortex and the reference-memory functions of the hippocampus. Further study is needed, however, to identify the structure or combination of structures responsible for the CMT effects observed in this study. Interestingly, haptic training reduced the relearning deficit after the large visual cortex lesions somewhat differently than haptic training after the more restricted lateral visual cortex lesions. The effectiveness of smooth S+ training had a greater effect on subsequent visual relearning with the larger lesion than with the smaller lesion, whereas the effectiveness of rough S+ training was diminished after large lesions but only with the dark visual cue, even though all rats responded similarly to both cues during haptic training. These results suggest that the larger lesion of the visual cortex had a greater impact on the processes responsible for transfer of specific information from the somatosensory system to the visual system, e.g., increasing the amount of transfer when training involved the smooth S+ while reducing the amount of relevant information transferred after training with the rough S+, particularly when the visual S+ was the dark stimulus. Thus, haptic training appeared to yield a general response strategy (e.g., reference memory) that was modality-independent as well as some sensory-specific information that, when transferred to the visual system, might facilitate retrieval processes or relearning during the postoperative visual relearning session. These hypotheses are currently being explored. The implications of the findings of these experiments are important. They expand the breadth of the potential for CMT-based intervention procedures to a different motivational condition (positive reinforcement vs. earlier shock-
avoidance paradigms) and to the two modalities (auditory/ visual and somatosensory/visual) that have received the most attention in CMT research. Previous work with nonhuman animals showing beneficial effects of CMT has primarily been with auditory and visual training cues. In addition, these effects have been seen most frequently when the postinjury training with each modality has been separated over days, as it was in this study. On the other hand, studies in humans, which have resulted largely in equivocal therapeutic results, have most often paired haptic with visual cues, typically either within the same session or in the same trial. The results of the present study indicate that the differences in modalities probably do not account for the lack of consistency between human and nonhuman studies. Nonhuman animal studies have shown that the temporal sequencing of the training can be a critical factor [24]. The data from this study show that somato-visual integration can aid recovery of at least some visually based cognitive functions and, in view of the clinical implications, the characteristics of and limitations to effective CMT training after brain injury need further exploration. In sum, haptic discrimination training after either lateral visual cortex or larger, more complete visual cortex lesions which included the anteromedial region of the visual cortex, facilitated relearning of a reinforced maze intensity discrimination. These results extend earlier reports showing CMT training enhances recovery of avoidance behavior after visual and auditory cortex lesions and indicate that CMT training after brain injury may have broader applicability for recovery of behavior than previously indicated. Postoperative CMT training such as the haptic discrimination training in this study results in the development of cognitive schema or reference memories that facilitate recovery of behavior learned preoperatively. More importantly, the principles derived from this and previous studies may lead to important intervention techniques that may be applicable in cognitive neuropsychological rehabilitation therapies.
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Postoperative haptic training facilitates the retrieval of visual-based memories after visual cortex lesions in rats M. Claire Cartford1, Annette J. Beaver, Katrina A. Wagner, Eugene R. Delay* Department of Psychology, Regis University, 3333 Regis Boulevard, Denver, CO 80221, USA Received 30 April 2002; received in revised form 9 December 2002; accepted 28 January 2003
Abstract Two experiments examined the effects of postoperative haptic discrimination training on the relearning of a maze visual discrimination in rats with visual cortex lesions. In the first experiment, rats learned a visual intensity discrimination prior to ablation of the lateral Oc2L cortex. Lesion rats were exposed to either a rough/smooth haptic discrimination training condition, a random training condition, or a notraining condition prior to relearning the visual task. Lesion rats relearned the visual task faster after haptic training than after other postoperative experiences. The second experiment replicated these procedures but with rats in which most of the visual cortex was removed. The lesion-induced relearning deficits in the second experiment were similar to the deficits seen for the smaller Oc2L lesions in the first experiment, supporting the hypothesis that the lateral visual cortex is critical for intensity discrimination. Haptic training also reduced these deficits, but the magnitude of this effect was related to the characteristics of the haptic cue. Postoperative training with haptic cues can produce specific and nonspecific information transfer from the intact somatosensory system to the damaged visual system that can facilitate the visual relearning. Possible implications for neuropsychological rehabilitation are also discussed. D 2003 Elsevier Science Inc. All rights reserved. Keywords: Visual discrimination; Haptic discrimination; Cross-modal transfer; Reference memory
1. Introduction In recent years, our understanding of the interrelationships between sensory modalities, cognitive function, and the functional organization of brain structures underlying these relationships have been advanced with modern imaging techniques and the study of brain-injured patients. For instance, a recent positron emission tomographic study revealed modality-specific and multimodal regions of the human brain active during tactile, visual, and tactile –visual discrimination tasks [1,2]. Others have identified attentional processes that can link common elements of different modalities during cognitive processing [3]. Awareness of the potential clinical relevancy of these relationships has been increased by studies of functions such as bimodal extinction in patients with cortical injuries (cf. Refs. [4,5]) and by the development of neurorehabilitation programs * Corresponding author. Tel.: +1-303-458-4976; fax: +1-303-9645527. E-mail address: [email protected] (E.R. Delay). 1 Present address: Center for Aging and Brain Repair, University of South Florida, Tampa, FL, USA.
that use sensory cues in more than one sensory modality. In these treatment programs, it is generally assumed that cues presented to undamaged sensory modalities support or reinforce the cues processed by the less efficient, damaged sensory modality. However, the success of these treatment programs has been moderate [6 – 8] or equivocal [9,10]. Research examining the effects of cross-modality transfer (CMT) of learning in brain-damaged rats may provide some insight into the efficiency and the generalization of multisensory rehabilitation approaches. CMT of discrimination learning involves the transfer of information from a task using cues in one sensory modality to a similar task subsequently learned using cues in a second modality [11]. For example, a subject learns first to discriminate between two visual stimuli of different intensities, and then learns to discriminate between two stimuli of different intensities in a second modality. CMT is seen if the rate of learning of the second discrimination is faster for this subject than for a control subject who did not receive experience with the first modality or who received experience with different but comparable stimuli. CMT can occur when the stimuli of the two modalities share common attributes such as temporal patterns or duration, location, or relative intensity [12 – 14].
0031-9384/03/$ – see front matter D 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0031-9384(03)00045-3
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The capacity for transfer between visual and auditory modalities in rats has been established with a variety of discrimination tasks [14 – 17]. Importantly, this capacity is at least partially accessible to brain-damaged rats [18] and is capable of aiding recovery of behavior following cortical injury. For example, in one study [19], rats learned an avoidance response when a visual intensity cue preceded shock. After ablation of the visual cortex, these rats were given similar avoidance training with an auditory intensity cue the day before relearning the visual discrimination. Surprisingly, these rats relearned the visual discrimination in significantly fewer trials than other lesion rats given equivalent training with the preoperative visual discrimination. More recent studies have reported similar findings for several behavioral tasks including recovery of temporal discriminations [20] and auditory discrimination behavior after auditory cortex lesions [21]. Moreover, postinjury auditory training not only substantially reduced large behavioral deficits seen with a visual serial reversal learning task, but also showed better generalization than training with the damaged visual system [22]. These findings suggest that postinjury CMT training has the potential to reduce a variety of neuropsychological deficits. To date, however, all of these studies used only auditory and visual stimuli within an active shock-avoidance paradigm. On the other hand, most of the research in CMT with brain-injured humans and monkeys has focused on interactions between the visual and somatosensory modalities (for a review, see Ref. [11]). Although several studies were unable to detect significant alterations in somato-visual CMT following cortical lesions (e.g., Refs. [26,27]), others observed somato-visual CMT but also found impaired CMT after either large cortical lesions or lesions involving the parietal cortex [28 –31]. Thus, the area of the cortex that is damaged might play a significant role in whether postoperative CMT training will be of benefit depending on the sensory modalities involved. Understanding the areas of the cortex that contribute to mnemonic processes that are accessible by multiple sensory modalities is important for developing successful CMT strategies for brain-injured patients. Studies of somato-visual CMT with rats are lacking, but if one considers bimodal conditioning studies, this capacity may be limited in rats with damage to certain areas of the cortex. For instance, lesions in the anterior region of Oc2M of the extrastriatal cortex blocked conditional learning with bimodal visual and somatosensory stimuli [32] and, after large posterior lesions, postoperative compound conditioning with haptic and intensity cues interfered with the relearning of a preoperatively acquired visual intensity discrimination [23]. These findings suggest that posterior cortical lesions, particularly if the anteromedial extrastriatal cortex is involved, may impair somatovisual integration and thus might limit the effectiveness of somatosensory CMT as a ‘‘rehabilitation therapy.’’ Our goal was to use postinjury CMT training to examine a
possible therapeutic role for somato-visual interrelationships in a rat model. Two issues were addressed in this study. The first questioned whether postoperative somatosensory training can influence recovery of visual intensity discrimination after visual cortex lesions that spare most of the anteromedial extrastriatal cortex. This experiment showed that postoperative haptic training reduced visual relearning deficits when lesions were limited to the lateral visual cortex. Because of these findings, a second experiment was conducted to determine whether large visual cortex lesions that included the anteromedial extrastriatal cortex, a multisensory region with somato-visual functions [32 –34], would block the effects of somatosensory CMT training. This experiment showed that postoperative haptic training was still effective in facilitating visual relearning but was much more dependent upon the characteristics of the haptic cue. Since the design of the two experiments were essentially the same, they are presented together.
2. Materials and methods 2.1. Subjects The subjects for the two experiments were 80 male, naive Sprague – Dawley albino rats which, by the first training session, were between 90 and 120 days old and weighed between 320 and 420 g. They were housed singly in their home cages with food available ad libitum. All rats were trained during the light portion of the 12:12 LD cycle. The rats were maintained on a 23-h water-deprivation cycle and were handled for 5 – 10 min each day for at least six consecutive days prior to the first training session. 2.2. Apparatus All rats were trained in a two-arm maze described previously [35]. The maze, painted black throughout, had a start box connected to a 25 25-cm choice area which, in turn, was connected to two adjacent arms 10 50 cm long, each ending with a goal area (see Fig. 1). The floors of the start box and goal areas were stationary, but either of two removable floors could be positioned under the choice area and the maze arms. One floor, designed to present visual stimuli, was made of two sheets of transparent Plexiglas hinged on one side. The floor was divided into two halves by placing black and white stimuli, each extending the length of the choice area and one of the maze arms, between the Plexiglas sheets. For the white stimulus, white translucent paper was illuminated from beneath the floor by rows of 40-W Softwhite incandescent lights. The intensity of these lights, controlled with a dimmer switch, was 45 lx (Calcu-Light light meter, Quantum Instruments) at 0.5 cm above this half of the floor. For the black stimulus, black nontranslucent paper was placed over the other half of the
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Fig. 1. The two-choice maze with the stimulus floor (with visual stimuli) removed from beneath the maze. A portion of the light array below the floor of the maze can be seen in the cutaway.
floor. Light intensity of this side, measured as reflected light 0.5 cm above the surface of the floor, were between 0.67 lx at 1 cm from the border of the white half of the floor and less than 0.033 lx at 1 cm from the outer wall. The second removable floor, made to present the haptic stimuli, was also divided lengthwise into halves by rough and smooth stimuli mounted to the top of brown pressboard. The haptic stimuli were made from K-lux Clear Prismatic (PTC-25) fluorescent light cover paneling that was smooth on one side and had a repeating pattern of peaks and depressions on the other side (see Fig. 2). The basic pattern was a square measuring 4.6 mm on a side. The highest points of the pattern, located at each corner, were 1.0 mm above the center and lowest point of the pattern. A water well was located on the floor of the goal area of each arm. A fan generated 50 ± 2 dB during all training sessions.
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could cumulate over two sessions. All trials were counted toward criterion. A random sequence for locating the S+ and S during each trial was determined prior to each training session. To prevent the development of a side preference, the S+ could not be located on the same side for more than three consecutive trials, unless the procedure for an erroneous response was used. The time interval between trials ranged from 30 to 60 s. The training session for each rat lasted about 20 min, and then the rat was given access to a water bottle in the home cage for 40 min. Surgery was performed 24 h after the rat reached the criterion. Each rat was given atropine sulfate (0.15 cc, 10 mg/cc ip) to minimize salivation during surgery and then was anesthetized with sodium pentobarbital (50 mg/kg ip). Sham-operated rats were closed after opening the cranium. For rats in the lesion groups, the cranium was removed from the area immediately over the appropriate cortical region, the meninges were opened, and the cortical tissue was removed bilaterally by suction. After the incision was sutured, the rat was given Crystiben (0.1 cc, 300,000 units/cc im) to prevent infection and then was monitored for any postoperative complications. After surgery, rats were given 6 days of recovery before returning to the 23-h water-deprivation schedule. On the eighth day after surgery, eight rats in each experiment were assigned to one of five groups. One group of rats, hereafter identified as the intact group, was comprised of the shamoperated (n = 4) and normal control rats (n = 4). This group and a group of lesion rats were assigned to a no-training condition in which the rats remained in the home cage until the relearning procedures. One group of lesion rats was assigned to each of two haptic training conditions; one group was trained with the smooth surface as the S+, and
2.3. Procedure Each rat was allowed to explore the maze for at least 10 min on a clear acrylic floor without stimuli or reinforcers for 2 days. This was followed by a day of magazine training and 2 days of alternation training before the start of discrimination training. During discrimination training, a trial began when the door of the start box was raised and the rat entered the choice area. The water well in each maze arm was hidden behind a stimulus door that matched the floor. If the rat advanced halfway down the S+ arm, the goal door was removed to give the rat access to 0.15 ml of a 10% sucrose solution (w/v) reinforcer. To ensure that the rat remained in the maze arm for 10 s, a door was inserted at the entrance of the arm. If the rat entered the S arm, the goal door was not removed, the rat had to remain in the arm for a period of 30 s, and the S+ and S stimuli remained on the same side of the maze during the next trial. During preoperative training, half of the rats were trained with the white stimulus as the S+ and half were trained with the black stimulus as the S+ until they reached a criterion of 18 correct responses out of 20 (18/20) consecutive trials. Each session consisted of 20 trials, and criterion responses
Fig. 2. The repetitive pattern of the acrylic material that served as the rough haptic stimulus. The upper portion of the figure is an enlargement of four squares of the pattern. Fundamentally, each square was a concave surface with a peak in each corner. The peaks, 4.6 mm apart (A), were connected via a curvilinear ridge. The bottom of the ridge (B) was 0.8 mm below the peaks, and the center of the square (C) was 1.0 mm below the peaks. The opposite side of the material (D) was a relatively uniform surface that was used for the smooth haptic stimulus.
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the second group was trained with the rough surface as the S+. During haptic training, the lights beneath the maze were turned off and a red light located above the apparatus provided 6 lx of reflected light for the experimenter. In previous research, intact rats did not respond to visual stimuli under these conditions [35]. To determine whether exposure to cues, habituation to the apparatus and training procedures, or other nondiscrimination variables might have an effect during transfer training, a fifth group of lesion rats was given random haptic training. Random haptic training was identical to standard discrimination training except that the locations of the stimuli and the reinforcer were varied independently of each other. The haptic stimuli were randomly assigned to each arm of the maze and could be assigned to the same arms for as many as five consecutive trials. The location of the reinforcer was also randomized but could not occur in the same arm for more than three consecutive trials. If the rat entered the maze arm without the reinforcer, the rat was forced to stay in that arm for 30 s. In addition, the reinforcer was automatically located in the same arm on the next trial, but the haptic stimuli were free to vary according to the preassigned random sequence. Presentation order of the stimuli was checked to make sure that no more than chance pairings of the reinforcer and either stimulus occurred on a given training day. Each group was counterbalanced so that half of the rats were trained with the white S+ and half were trained with the black S+ during the preoperative session. Rats in the two haptic conditions and in the random training conditions were given 20 trials each day for 2 days. Ten days after surgery, each rat began retraining with the preoperative visual stimuli and was given 20 trials per day until it reached the 18/20 criterion. After each lesion rat reached the criterion for relearning, it was given an overdose of Nembutal, perfused with saline and then 10% formal saline, and the brain tissue was removed. Two independent observers mapped the extent of each lesion and quantified the area of each lesion with a grid overlay. Any discrepancies between the two maps were resolved before the tissue was frozen, sectioned at 20 um, and every 10th section stained with fast blue and cresyl violet for microscopic examination.
3. Results 3.1. Histological results 3.1.1. Experiment 1 The largest and smallest lesions of the lateral visual cortex are shown in Fig. 3. The following assessments of the lesions are based on Zilles and Wree’s [36] descriptions of the posterior cortical areas of the rat. These lesions included nearly all of the lateral aspects of Oc2L in every rat. The medial edge of the lesion infringed slightly into Oc1B and spared the anteromedial portion of Oc2L immediately rostral to Oc1. The anterior extent of the lesion was
Ent
Fig. 3. The largest (stipple) and smallest (hatch) lesions of the lateral visual cortex in Experiment 1.
the most variable aspect of the lesions but invaded the posterior region of Par1 in every instance. In every case, the ventrolateral boundary of these lesions included the rostral areas of Te2 and Te3 adjacent to Oc2L and most encroached into the rostral region of Te1. These lesions also included some portion of the posterior perirhinal cortex (PRh), and a few extended into the posterior entorhinal area (Ent). Within these boundaries, the lesions extended into, but not through, the underlying radiations, and no damage to underlying subcortical structures was detected. Degeneration was detected in the dorsal lateral geniculate nucleus and the lateral posterior nucleus of the thalamus. Analysis of the areal measurements of the lateral lesions indicated that, on average, 5% of the tissue along the lateral and ventral edges of Oc2L was spared. Grid counts indicated that, on average, 15% of the anteromedial Oc2L was
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spared. Analysis of variance (ANOVA) did not find any group difference in estimated lesion size or in the amount of tissue spared [ F’s < 1.0]. 3.1.2. Experiment 2 The largest and smallest cortical lesions of the second experiment can be seen in Fig. 4. The lateral and posterior boundaries of these lesions were essentially the same as those described for Experiment 1. In addition, every lesion encompassed all of the anteromedial portions of Oc2L and all of Oc1 and Oc2M. The medial edge of these lesions invaded the lateral agranular retrosplenial cortex (RSA). The anterior portion of these lesions extended into the posterior area of the frontal areas Fr1 and Fr2, the primary somatosensory cortex (Par1), and included up to half of the hindlimb (HL) area. No lesion, however, extended into the
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forelimb area (FL). All lesions extended into, but not through, the underlying radiations. No damage to the underlying subcortical structures was detected. Degeneration was seen in the dorsal and ventral lateral geniculate, lateral posterior, and lateral dorsal thalamic nuclei. Areal measurements of the full lesions showed that less than 1% of the Oc1 and Oc2 areas were spared. ANOVA procedures did not detect any group differences in estimated lesion size or in the amount of tissue spared [ F’s < 1.0]. 3.2. Behavioral results In both experiments, the preoperative learning and postoperative relearning scores, representing the number of trials to criterion, were adjusted before analysis by subtracting 20, the learning criterion. Then the data for each experiment were subjected to ANOVA procedures and to post hoc and simple-effects tests, as needed. 3.2.1. Experiment 1 The analysis of the data for the rats with lesions of Oc2L revealed significant effects of pre- and postoperative visual discrimination sessions [ F(1,30) = 18.86, P < .001], postoperative haptic training conditions [ F(4,30) = 10.29, P < .001], and the interaction between these two variables [ F(4,30) = 18.96, P < .001; see Fig. 5]. One-way ANOVA indicated that trials to criterion for the five groups did not differ during the preoperative session [ F < 1.0] but differed significantly during the relearning session [ F(4,35) = 35.00, P < .001]. Simple-effects tests indicated that the random training and the notraining lesion groups required significantly more trials to reach criterion during the relearning session than during preoperative learning, whereas intact no-training and the two haptic discrimination groups required significantly fewer trials (all P’s < .025 or smaller). Newman– Keuls comparisons ( P < .05) of the relearning data showed that lesion groups in the random training and the no-training conditions took significantly more trials to reach criterion than the other three groups and that the scores of the rats given training with the smooth S+ were significantly higher than the scores of the rats trained with the rough S+. No analysis found any differences between light and dark S+. Finally, the scores of the intact group were significantly smaller than all other groups.
Fig. 4. The largest (stipple) and smallest (hatch) lesions of the visual cortex in Experiment 2.
3.2.2. Experiment 2 The ANOVA for the preoperative and postoperative visual discrimination data of the groups with large cortical lesions found significant main effects for postoperative haptic training conditions [ F(4,30) = 13.05, P < .001], sessions [ F(1,30) = 15.24, P < .001], and interactive effects between these two variables [ F(4,30) = 15.20, P < .001; see Fig. 6]. Separate analyses of scores for the pre- and postoperative sessions did not detect group differences in preoperative learning [ F < 1.0], but did for the scores of the second session [ F(4,35) = 20.09, P < .001]. Simple-effects
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relearned their visual discrimination in significantly fewer trials than the dark S+ group ( P < .001; see Fig. 6).
Fig. 5. The mean (S.E.M.) trials to criterion, less the criterion trials, for preoperative learning and postoperative relearning of the intact and lesion no-training groups and the random, smooth, and rough S+ haptic groups with lateral cortex lesions (Experiment 1).
tests ( P < .01) comparing the scores for the pre- and postoperative visual discrimination sessions showed that the postoperative trials to criterion scores of the intact control group and the two haptic lesion groups were significantly lower than their respective preoperative scores, whereas the postoperative scores of the random training and the notraining lesion groups were significantly higher than their preoperative scores. Newman –Keuls comparisons ( P < .05) showed that the intact control rats and the two groups of rats given haptic training had significantly better scores during the relearning session than the no-training and the random training lesion groups. Also, the intact rats had significantly lower scores than rats given postoperative training with the rough S+. In addition, a t test indicated that the light S+ group given postoperative training with the rough S+
Fig. 6. The mean (S.E.M.) trials to criterion, less the criterion trials, for preoperative learning and postoperative relearning of the rats conditioned with the light and dark S+ cues for each training group with large visual cortex lesions (Experiment 2). Training groups included the intact and lesion no-training groups and the random, smooth, and rough S+ haptic groups.
3.2.3. Comparisons across experiments The results of the individual experiments suggested that the effects of haptic training depended upon the nature of the visual S+ and the lesion. To test this, the scores of the rats trained with the smooth and the rough S+ in each experiment were compared. Although the design and execution of the two experiments were assumed to be equivalent, analysis of the preoperative learning scores indicated rats in the first experiment learned the visual discrimination in significantly fewer trials (mean = 24.00, S.E.M. = ± 2.35) than rats in the second experiment (mean = 31.00, S.E.M. = ± 1.22) [ F(1,24) = 7.43, P < .025]. Consequently, the data of each rat were normalized by dividing the relearning score by the preoperative learning score. This procedure generates a proportional score which, if less than 1.0, indicates retention of the task during relearning [19 –21,24]. An ANOVA of these scores revealed a significant three-way interaction between training conditions, the intensity of the visual cue, and the two lesions [ F(1,24) = 11.92, P < .001]. Newman– Keuls tests indicated that rats with the large lesions trained with the dark S+ and with the rough S+ during experimental training, required significantly more trials to relearn the visual discrimination than all other groups. Of the remaining groups, rats with lateral lesions trained with the light S+ and given postoperative training with either haptic S+ relearned the task in significantly more trials than the rats in the other conditions (see Fig. 7). Thus, the effects of postoperative haptic training conditions on relearning were dependent upon all three variables. Finally, neither the size of the lesion nor the amount of the target area was not correlated with the proportional scores (all r’s < .20).
Fig. 7. Mean (S.E.M.) proportional scores (relearning scores/preoperative learning scores) for rats with lateral visual cortex lesions (Experiment 1) and large lesions (Experiment 2) that were given smooth and rough haptic S+ training the day before relearning began.
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3.2.4. Experimental training Reinforced responses during experimental training were analyzed to examine the effects of lesion size (2), visual S+ (2), and haptic training condition (3). This ANOVA found a significant effect of training condition on reinforced responding [ F(2,36) = 12.28, P < .001]. Post hoc comparisons showed the groups given random training emitted significantly fewer reinforced responses (mean = 13.17, S.E.M. = 0.81) than those emitted by the rats given haptic training with either smooth (mean = 20.63, S.E.M. = 1.10) or rough S+ (mean = 19.44, S.E.M. = 1.17). In addition, the level of learning reached during haptic training was examined by determining the highest number of reinforced responses in 20 consecutive trials reached by the rats in both experiments. The analysis of these data indicated that haptic training condition was the only variable to significantly alter the level of learning with haptic cues [ F(2,21) = 4.43, P < .01]. Rats trained with the smooth and rough S+ reached significantly higher criteria of learning (smooth: mean = 11.94, S.E.M. = 0.61; rough: mean = 12.01, S.E.M = 0.65) than the rats in the random training condition (mean = 8.39, S.E.M. = 0.39). In summary, both lesions produced similar deficits during postoperative relearning. Random training procedures did not significantly alter the relearning deficit induced by either lesion. In contrast, training with either the rough or smooth S+ reduced relearning deficits, although not necessarily in an equivalent manner for the two visual intensity cues. After lesions of Oc2L, training with the rough S+ reduced the relearning deficit more than training with the smooth S+ with either visual cue. However, the rough S+ was much less effective at reducing the lesion deficit for rats with the large lesions trained with the dark S+ compared to all other conditions.
4. Discussion In these experiments, we sought to use a visual intensity discrimination learning model in the rat to examine potential effects of CMT between visual and somatosensory systems. The visual discrimination in this study differs somewhat from the two-choice maze discrimination tasks typically used in that the discriminative stimuli were located on the floor of the maze rather than as part of a vertically oriented display of either doors at or near the entrance of the maze arms or lights located somewhere within the arm. Replicating previous observations [35], the intact rats in this study readily learned and relearned this discrimination. Relearning deficits after lesions of the lateral visual cortex and after the larger, more complete lesion of the visual cortex, were comparable; that is, after either lesion relearning scores averaged approximately 50% higher than preoperative scores. The magnitude of the relearning deficits for these two lesions are relatively similar to each other even though the full lesions were much larger than the lateral lesions,
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ruling out explanations such as mass action. These findings agree with previous reports [37] and support the notion that the lateral area of Oc2L, an area particularly important for spatial contrast sensitivity [38], is the area of the rat’s visual cortex most involved in the retention of intensity discrimination within a maze task [37,39]. Haptic discrimination training reduced relearning deficits after either lateral or large visual cortex lesions. These findings are in agreement with earlier studies in which postoperative CMT training with an intact sensory modality reduced lesion deficits in retention and reversal learning of visual or auditory shock-avoidance tasks [19 – 22,24]. The positive effects of haptic training apparently are not the results of additional handling, habituation to the test apparatus, or exposure to testing procedures since relearning of the lesion rats in the random haptic training condition did not differ from the lesion rats in the no-training condition. Rather, training with either the smooth or rough S+ may have involved ‘‘multimodal’’ [12] or ‘‘amodal’’ [13,40,41] processes responsible for much of the beneficial effects of postoperative CMT training. A key characteristic of CMT, one that differentiates CMT from bimodal compound conditioning or conditional discrimination, is the temporal separation between the cues of the two modalities. In CMT, the temporal separation between training sessions allows the brain-injured rat to develop a reference memory or schema with the intact modality without biasing the rat away from using the damaged sensory system as it does during bimodal compound conditioning when cues are simultaneous and redundant [23,24]. Thus, during relearning, the lesion rat can draw on the schema as a functional compensatory mechanism to help retrieve preoperative memories of the visual discrimination task with the damaged neurological system [24,25]. The beneficial effects of haptic training on visual relearning seen in this study extend this notion to postoperative training with somatosensory cues in rats with lesions of the visual cortex. Although the positive effects of haptic CMT were expected after the lateral visual cortex lesions, the effects of haptic training on visual relearning following the large lesions were surprising. After the removal of the lateral visual cortex, cortical tissue between the somatosensory and the primary visual cortex remained intact and presumably could serve as the neurological basis for multimodal integration and transfer of learning between the somatosensory and the visual modalities. Others have found that unilateral damage to the posterior parietal area results in contralateral multimodal neglect [42,43]. Bilateral damage to the anterior portion of Oc2M disrupts bimodal somato-visual conditional discrimination ability [32] and lesions of the posterior parietal cortex blocks visual –auditory transfer when tasks involve spatial relationships [44]. Additionally, lesions of the posterior parietal region in rats impaired retention, but not acquisition, of an intensity discrimination (described as Areas 7, 39, and caudal 2 [37]). Collectively, these findings suggest that the
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cortex between the visual and somatosensory cortices, although probably not directly crucial to performing a visual intensity discrimination [37], is functionally important as a multimodal sensory association area [45]. While the results of the first experiment can be explained by this hypothesis, the results of the second experiment cannot, since the large lesions were deliberately extended into nearly all of the extrastriatal cortices, the posterior parietal cortex, and the striate cortex. Spared tissue surrounding the lesion, other cortical or subcortical structures of the visual system receiving multisensory input such as the visual region of the temporal cortex [33,34,46] or the superior colliculus [25], or other multimodal structures, may have been responsible for the effects of the postoperative haptic training on visual relearning in this study. A number of areas of the brain have been identified where CMT occurs but many of these multimodal structures such as the amygdala are involved in CMT only if they are closely related anatomically and functionally to the cognitive functions essential for the behavior. The CMT effects in this study may be functionally related to cross-modal memory functions associated with the frontal cortex [47 – 49], the amygdala [50,51], or the hippocampus [51 – 54]. It is also conceivable that more than one area might combine cross-modal functions such as the working memory functions of the frontal cortex and the reference-memory functions of the hippocampus. Further study is needed, however, to identify the structure or combination of structures responsible for the CMT effects observed in this study. Interestingly, haptic training reduced the relearning deficit after the large visual cortex lesions somewhat differently than haptic training after the more restricted lateral visual cortex lesions. The effectiveness of smooth S+ training had a greater effect on subsequent visual relearning with the larger lesion than with the smaller lesion, whereas the effectiveness of rough S+ training was diminished after large lesions but only with the dark visual cue, even though all rats responded similarly to both cues during haptic training. These results suggest that the larger lesion of the visual cortex had a greater impact on the processes responsible for transfer of specific information from the somatosensory system to the visual system, e.g., increasing the amount of transfer when training involved the smooth S+ while reducing the amount of relevant information transferred after training with the rough S+, particularly when the visual S+ was the dark stimulus. Thus, haptic training appeared to yield a general response strategy (e.g., reference memory) that was modality-independent as well as some sensory-specific information that, when transferred to the visual system, might facilitate retrieval processes or relearning during the postoperative visual relearning session. These hypotheses are currently being explored. The implications of the findings of these experiments are important. They expand the breadth of the potential for CMT-based intervention procedures to a different motivational condition (positive reinforcement vs. earlier shock-
avoidance paradigms) and to the two modalities (auditory/ visual and somatosensory/visual) that have received the most attention in CMT research. Previous work with nonhuman animals showing beneficial effects of CMT has primarily been with auditory and visual training cues. In addition, these effects have been seen most frequently when the postinjury training with each modality has been separated over days, as it was in this study. On the other hand, studies in humans, which have resulted largely in equivocal therapeutic results, have most often paired haptic with visual cues, typically either within the same session or in the same trial. The results of the present study indicate that the differences in modalities probably do not account for the lack of consistency between human and nonhuman studies. Nonhuman animal studies have shown that the temporal sequencing of the training can be a critical factor [24]. The data from this study show that somato-visual integration can aid recovery of at least some visually based cognitive functions and, in view of the clinical implications, the characteristics of and limitations to effective CMT training after brain injury need further exploration. In sum, haptic discrimination training after either lateral visual cortex or larger, more complete visual cortex lesions which included the anteromedial region of the visual cortex, facilitated relearning of a reinforced maze intensity discrimination. These results extend earlier reports showing CMT training enhances recovery of avoidance behavior after visual and auditory cortex lesions and indicate that CMT training after brain injury may have broader applicability for recovery of behavior than previously indicated. Postoperative CMT training such as the haptic discrimination training in this study results in the development of cognitive schema or reference memories that facilitate recovery of behavior learned preoperatively. More importantly, the principles derived from this and previous studies may lead to important intervention techniques that may be applicable in cognitive neuropsychological rehabilitation therapies.
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