Physioh~gy & Behavh,r, Vol. 22, pp. 139-147. Pergamon Press and Brain Research Purl., 1979. Printed in the U.S.A.
Tactile Discrimination Performance Deficits Following Neglect-Producing Unilateral Lateral Hypothalamic Lesions in the Rat L E E H O Y M A N , G. D A N I E L W E E S E , A N D G A B R I E L P. F R O M M E R I
Psychology Department, Indiana University, Bloomington, IN 47401 (Received 19 M a y 1978) HOYMAN, L., G. D. W E E S E AND G. P. FROMMER. Tactile dis('riminution perfi~rmun('e defi('its following neglec'tproducing unilateral lateral hypothalumic lesions in the rut. PHYSIOL. BEHAV. 221 I) 139-147, 1979.--Unilateral lesions of the lateral hypothalamus (LH) which produced pronounced asymmetries on a battery of neurologic tests also produced a pattern of deficits on three appetitive tactile discrimination tasks which suggested a response deficit rather than "sensory neglect." Deprived rats trained to turn toward a gentle touch to the flank to obtain sugar water were selectively impaired only when touches were presented contralateral to the lesion. A second group of rats trained to turn away from the side of the touch was only impaired when the touch was ipsilateral (and the response contralateral) to the lesion. A third group of rats trained to make the same forward-directed response following a touch on either flank was not impaired when either side was touched. Thus, across the three tasks, performance on trials in which touches were contralateral to the lesion was not impaired unless the response was also contralateral, and contralateral responses were always impaired regardless of where the touch occurred.
Neglect Sensory neglect Tactile discrimination
Orienting
LH lesions
SEVERAL recent theoretical formulations [5, I0, 11, 14, 24, 29, 30, 31] have proposed that the lateral hypothalamus (LH) influences behavior by facilitating the sensory and motor systems or sensorimotor coordinations involved in the expression of particular motivated behaviors and by inhibiting those processes related to irrelevant behaviors. In several of these theories this sensorimotor modulation is seen as the physiological basis of such behavioral concepts as "motivation" or "drive." Thus, according to this view when an animal is "hungry," its food-getting sensorimotor systems are tuned to be especially responsive to food-related stimuli. Several lines of evidence are consistent with this conception. The most compelling evidence has come from LH stimulation studies, particularly those demonstrating intensity dependent enlargements of the tactile sensory fields for eliciting attack-related behaviors (paw-batting, head-turning, and mouth-opening) in the cat [3,19]. Other studies with rats have shown selective stimulation-induced increases in responding to produce a dim light [1] and in responding to a food-predictive light cue contralateral to unilateral stimulation [4]. Finally, weak support for the view that LH stimulation facilitates sensorimotor processes can be derived from the observation that LH-stimulation-induced stereotyped behaviors can be switched to other behaviors by changing the exteroceptive stimulus environment of the animal [27].
Feature-negative discrimination
Analogous suggestions have been made that sensorimotor inattention, sensory neglect, or sensory deficits follow LH lesions [20, 21, 22, 28]. However, most of the behavioral observations in these studies utilized simple neurological tests such as the failure of the orientation response to contralateral stimuli. Such tests do not operationally isolate sensory or other processes except through non-spatial aspects (respiration, heart rate) of the orienting reaction. Turner [26], using a learned task that did make such a separation, found what he interpreted to be deficits in intrahemispheric sensorimotor integration following unilateral LH lesions. He trained restrained rats to escape shock to one hindpaw by making a head-turning response. Half of the rats were trained to turn away from the side of the shocked paw, thereby presumably separating primary mediation of sensory (and motivating) events and response execution processes to opposite hemispheres. The remaining rats were trained to turn toward the side of the shock, thereby confining sensory and response processes to the same hemisphere. A deficit occurred only in those rats trained with the stimulus and response on the same side, contralateral to the lesion, suggesting a sensorimotor impairment. Additional supporting evidence has been reported in a response suppression task [32,33]. Cats with unilateral LH lesions were found to be most deficient in the suppression of licking when shock
'This research was supported by PHS grants MH 26973 and S05 RR 7031 to Gabriel P. Frommer. A shorter version of this research was presented at the Society for Neuroscience meetings, 1977 [18].
Copyright ~ 1979 Brain R e s e a r c h Publications Inc.--0031-9384/79/010139-09502.00/0
141)
HOYMAN, WEESE AND FROMMER
predicting visual cues were presented in the visual field contralaterai to the lesion. However, other experiments [2,8] have shown that while rats were unable to perform a contraversive escape response in a T-maze, they were able to make full use of contralateral visual information if a forward-directed avoidance response was required. Since most of the above studies employed aversive shock, the present study sought to examine the effects of unilateral LH lesions on purely appetitive discrimination performance. Three different tactile discrimination tasks which differed in the spatial relations between the discriminative stimuli and the instrumental responses were used in an attempt to isolate operationally sensory and response processes. The effects of the lesions on these tasks were then compared to the effects of the same lesions on a battery of neurologic tests similar to those used in previous neglect studies. EXPERIMENT 1
In this experiment the effects of unilateral L H lesions were examined on an appetitive task in which 0.5 g touch stimuli were applied randomly to the right or left flank, and a correct response was a head-turn toward the same side as the touch. This task represented the control condition in which all relevant processes were confined to the same hemisphere on each trial. The rats were also tested on a neurologlc battery derived from that used by Marshall and co-workers to define the phenomenon of sensory neglect [21,22].
Method Animals. Five female Simonsen hooded rats weighing approximately 200 g at the time of surgery were trained and lesioned. The rats were doubly housed prior to surgery and singly housed tbercafter in an artificially lighted room which was darkened for 12 hr at night. During training and testing the rats were allowed 15 rain access to water after each d a y ' s session and had constant access to Purina rat chow. Apparatus. Discrimination training took place in a 17×9x I 1 cm clear plastic chamber, the sides of which had 10x8 cm holes interrupted by vertical plastic rods spaced 3 cm apart. The floor was made o f stainless steel rods spaced 2 cm apart. Thrt~ 1.3-cm dia. holes, one centered in the front walt 6 cm from the floor and one on each side wall 6 cm from the floor and 2 cm from the front wall. had photocells iVector VT241) and 28 V miniature lamps (No. 327) positioned to detect nose-poke responses. Behind each side hole was a drinking tube filled with 8% sucrose solution which was accessible only wben a circular aluminum door was rotated open by a 30 rev/min clock motor, A drinkometer circuit between the drinking tubes and the grid floor recorded licks on the tubes. Tactile stimuli were presented manually by the experimenter by means o f Von Frey hairs made of 0.15-ram dia. piano wires approximately 15 cm long. Each was ~ to a plastic handle and had a 2-ram dia. styrofoam bali cem4mted on the end. The force of each o f the hairs was calibrated by varying the length of the unattached wire until it bent at the desired force. During each exporin~ntal session the exl~rireenter sat with Von Frey hairs poised in both hands which were resting on soft pads situated at the level of the open sides of the chamber. Colored lights cued the experimenter to touch the rat's flank through the bars of the chamber on either the right or left side. BRS 200 series solid state pro-
gramming equipment controlled access to the drinking tubes. cued the experimenter to present stimuli, and recorded response events on both counters and a four channel paper tape event recorder. Stimulus presentations were made according to one of three semirandom sequences originally generated by a computer program using the rules set forth by Fellows [91 for minimizing nondiscriminative strategies such as position biases, alternation, and win-stay, lose-shift. The action of the event recorder and counters was delayed until after the rat made a response to prevent the tactile stimuli from being confounded with auditory cues. Surger3,. Prior to training each rat was implanted with a chronic unilateral electrode aimed at the LH which was later used to produce a lesion. Each rat received IP injections of 5 mg methylatropine followed by a mixture of pentobarbital, magnesium sulfate, and chloral hydrate (Equi-Thesin or Chlor-Pent, 2.5 ml/kg) to induce anesthesia. The rat was blinded by enucleation to prevent it from seeing the delivery of the touch in the task. Then the head was fixed in a stereotaxic instrument which positioned the top of the skull horizontally [121 and the skull was exposed and carefully cleaned and dried. After a thin layer of dental cement (Caulk, Grip, Ivory) was applied, a hole was drilled in the skull, and a single strand electrode of Teflon coated 0.17-ram dia. stainless steel with only the cross section exposed at the tip was implanted 3.0 mm caudal to bregma, 2.0ram lateral to the midline, and 7.6 mm below dura and was fixed to the skull with dental cement. Procedure. After recovering from the electrode implantation, each rat was adapted to having 15 rain access to water each day and was shaped to lick the 8% sucrose solution from each of the two drinking tubes. Usually, 15 min shaping for two or three days was sufficient to stabilize the licking rate but not sufficient to extinguish random nose-poke responses in the center hole in the front wall. Following shaping, the automated tactile discrimination program began, During initial training, each session continued until the rat had obtained 12 reinforcements on each tube (correction procedure). To initiate trials (stimulus presentations) the rat was required to make an observing response in the center hole following a period of 3 sec or longer with no responses in any of the three holes. Trials began with the experimenter briefly touching the rat's middle flank between the front and hind legs with a 0.5 g Von Frey hair on either the right or the left side. If the rat was touched on the right side and broke the photocell beam in the right hole within 5 sec, the tube access door opened for 5 sec (timed from the first tongue contact with the sucrose tube). Similarly, a touch on the left followed by a response to the left was rewarded with 5 sec of licking on the left tube. An error of omission was defined as a failure to respond in one of the side holes within 5 sec after the experimenter presented the touch stimulus (and simultaneously pressed a foot pedal which signaled to the program the moment o f presentation of the touch). Responding in the hole opposite to the touched flank within the 5-sec period w a s an error of commission. As the rats approached the baseline criterion of no more than one error per session for three consecutive days, a noncorrection procedure was initiated and continued for the duration of the experiment, whereby the rat was presented with exactly 24 trials each session. Immediately after achieving criterion each rat was anesthetized with ether, and 2.0 mA anodal current was passed through the implanted electrode for 20 sec. If no obvious symptoms of neglect appeared on
TACTILE DISCRIMINATION DEFICITS FOLLOWING LH LESIONS the neurologic tests on the subsequent day, a second identical amount of cmrent was pasted t h r o u ~ the electrode, and the rat was retested on the discrimination. After the usual twenty-four 0.5 g stimulus presentations of the session, the data were recorded, and several additional trials were run. An ascending series of touch intensities (1, 2, 4, 8, and 16 g) was presented on the side where errors, if any, had occurred until either a ~ response was made or the 16 g touch failed to produce a correct response. An additional test trial in which two 0.5 g touches were simultaneously presented on both sides was included if few errors occurred on either side during the initial 24 trials. The rat was tested in this fashion for four successive days after the lesion, and intermittently thereafter. Each rat underwent a battery of neuroiogic tests just before its di~'~rimination session on at least 3 occasions prior to the lesion and on testing days following the lesion. The rats were always tramported to the testing room in their home cages so that the orientation tests, which ware performed with the rat in its home cage, could be performed before handling the rat ou that day. We have found that the orienting response to a tactile stimulus is very reliable and brisk when teated in an enclosed space, especially the home cage. Testing on an open platform, as did Marshall and ¢,oworkers, requires extended "training," and responses under these conditions remain less vigorous and reliable in our hands. A small, soft paintbrush with a 20-cm long handle was used to test orienting to light tactile stimuli. By carefully and noiselessly moving the brush through the wire of the home cage the experimenter lightly touched the rat on either the snout, shoztMer area, lower foreleg, middle flank, rear flank, or lower hindiq. Orientation responses were judged as "strong" if the rat turned toward or bit the probe, as " w e a k " if any movement at all in the direction of the probe occurred, and as "absent" if no movement or movement away from the probe occurred. A 27x37 cm elliptical platform was used for observation of open field locomotor behavior. Besides noting general posture and the amount of locomotion, the experimenter kept a record of the number of tarns made to ceeh side during a l-rain period beginning when the rat was placed on the field. As a further test of body side preference the rat was suspended by the tail and the direction it twisted its body in climbing its tail was noted. Also, each rat was allowed to hang by its forepaws from a horizontal rod in order to note which paw released its grip first. These tests taken together served as the main criteria for determining the presence of the "sensory neglect" syndrome, although various other tests and observations were often made. Histology. After testing had been completed, the rats received an overdose of anesthetic and were perfused intracardially with isotonic saline followed by 10% formol--saline. The brains were extracted, and frozen slices 40 /~ thick were made through the extent of the lesions. The sections were mounted and stained with cresyl violet. Photographic prints were made of key sections on Kodabromide F-5 paper by using the stained section as a negative in a photographic enlarger. A No. 8k2 Wratten filter was used to remove the blue and violet wavelengths from the light source of the enlarger in order to prevent the violet of the stain from exposing the photographic paper and decreasing the contrast. Data analysis. Mean performance for all measures was defined as the mean for the 3 days preceding and the 3 days immediately following the lesion. The ITI responses were
141
obtained from a paper tape record and were manually tabulated with the provision that very rapid sequences of responses were not to he considered separate r e d s unless the white of the paper showed between the pen marks (requiring about 0.5 sec separation). Statistical analyses were made by means of matched group two tailed t-tests which simply compared the mean performance of each of the rats before the lesion to its mean performance after the lesion. Every t-test was made with 3 degrees of freedom since four rats always provided the final data.
Results and Discussion Anatomy. Figure 1 illustrates the lesions in the four rats which completed testing. They were all located in the caudal 2/3 of the lateral hypothalamus. Rats 2 and 3 displayed neuroioocal asymmetries foliowing a s i n l k stage lesion that damaged the lateral part of the LH, the medial ~ of the internal capsule, and the subea_Osular region. Of the remaining 2 rats requiring 2 stage lesions, Rat 1 sustained the most extensive damage involving virtually all of the LH, an approximately equal amount of the internal capsule, and a small amount of the subcapsular region. Rat 4 sustained damage to most of the LH, a lesser amount of the internal capsule, and most of the subcapsular region. A fifth rat with an even more extensive lesion showed signs of general debilitation and was dropped from further consideration because it made only a few observing responses in the task on the first three postlesion days. Neurologic tests. All 4 rats displayed a nearly total failure to orient toward light touches anywhere on the flank, snout, or legs on the side contralateral to the lesion. Prior to the lesion, 96% of all touches resulted in a response rated as "strong." Following the lesion, 100% of the touches to the ipsilateral side produced a "strong" response, while 2% of the touches to the contralateral side produced a "strong" response, 13% produced a " w e a k " response, and 85% resuRed in an "absent" rating. A notable exception to this trend occurred in the most severely affected animal, Rat I, on the fwst day following the lesion. This rat reliably responded to contralateral touches by circling away from the probe while at the same time displaying a violent enhanced responsiveness to ipsilateral touches. Occasional instances of increased biting and chasing of the probe seen in the remaining rats suggested that enhanced responsiveness ipsilateral to the lesion may have occurred to some extent in all of the rats. Asymmetries were also quite evident during open field locomotion. Preoperatively the rats made a mean of 6.2 contraversive turns and 6.3 ipsiversive turns in the first rain on the open field, while postoperatively only 2.3 contraversive turns and 11.0 ipsiversive turns were made. The other neurological tests produced the same general result, enhanced responsiveness ipsilaterai and decreased responsiveness contralateral to the lesion. Some grooming and locomotor responses were usually observed on the ipsilaterai side. Thus, our lesions in conjunction with our neurological tests produced results closely similar to those reported in previous studies [22] Tactile discrimination. The unilateral LH lesions produced a selective deficit on only half of the trials of the discrimination. The mean number of correct responses decreased significantly (p
Tactile Discrimination Performance Deficits Following Neglect-Producing Unilateral Lateral Hypothalamic Lesions in the Rat L E E H O Y M A N , G. D A N I E L W E E S E , A N D G A B R I E L P. F R O M M E R I
Psychology Department, Indiana University, Bloomington, IN 47401 (Received 19 M a y 1978) HOYMAN, L., G. D. W E E S E AND G. P. FROMMER. Tactile dis('riminution perfi~rmun('e defi('its following neglec'tproducing unilateral lateral hypothalumic lesions in the rut. PHYSIOL. BEHAV. 221 I) 139-147, 1979.--Unilateral lesions of the lateral hypothalamus (LH) which produced pronounced asymmetries on a battery of neurologic tests also produced a pattern of deficits on three appetitive tactile discrimination tasks which suggested a response deficit rather than "sensory neglect." Deprived rats trained to turn toward a gentle touch to the flank to obtain sugar water were selectively impaired only when touches were presented contralateral to the lesion. A second group of rats trained to turn away from the side of the touch was only impaired when the touch was ipsilateral (and the response contralateral) to the lesion. A third group of rats trained to make the same forward-directed response following a touch on either flank was not impaired when either side was touched. Thus, across the three tasks, performance on trials in which touches were contralateral to the lesion was not impaired unless the response was also contralateral, and contralateral responses were always impaired regardless of where the touch occurred.
Neglect Sensory neglect Tactile discrimination
Orienting
LH lesions
SEVERAL recent theoretical formulations [5, I0, 11, 14, 24, 29, 30, 31] have proposed that the lateral hypothalamus (LH) influences behavior by facilitating the sensory and motor systems or sensorimotor coordinations involved in the expression of particular motivated behaviors and by inhibiting those processes related to irrelevant behaviors. In several of these theories this sensorimotor modulation is seen as the physiological basis of such behavioral concepts as "motivation" or "drive." Thus, according to this view when an animal is "hungry," its food-getting sensorimotor systems are tuned to be especially responsive to food-related stimuli. Several lines of evidence are consistent with this conception. The most compelling evidence has come from LH stimulation studies, particularly those demonstrating intensity dependent enlargements of the tactile sensory fields for eliciting attack-related behaviors (paw-batting, head-turning, and mouth-opening) in the cat [3,19]. Other studies with rats have shown selective stimulation-induced increases in responding to produce a dim light [1] and in responding to a food-predictive light cue contralateral to unilateral stimulation [4]. Finally, weak support for the view that LH stimulation facilitates sensorimotor processes can be derived from the observation that LH-stimulation-induced stereotyped behaviors can be switched to other behaviors by changing the exteroceptive stimulus environment of the animal [27].
Feature-negative discrimination
Analogous suggestions have been made that sensorimotor inattention, sensory neglect, or sensory deficits follow LH lesions [20, 21, 22, 28]. However, most of the behavioral observations in these studies utilized simple neurological tests such as the failure of the orientation response to contralateral stimuli. Such tests do not operationally isolate sensory or other processes except through non-spatial aspects (respiration, heart rate) of the orienting reaction. Turner [26], using a learned task that did make such a separation, found what he interpreted to be deficits in intrahemispheric sensorimotor integration following unilateral LH lesions. He trained restrained rats to escape shock to one hindpaw by making a head-turning response. Half of the rats were trained to turn away from the side of the shocked paw, thereby presumably separating primary mediation of sensory (and motivating) events and response execution processes to opposite hemispheres. The remaining rats were trained to turn toward the side of the shock, thereby confining sensory and response processes to the same hemisphere. A deficit occurred only in those rats trained with the stimulus and response on the same side, contralateral to the lesion, suggesting a sensorimotor impairment. Additional supporting evidence has been reported in a response suppression task [32,33]. Cats with unilateral LH lesions were found to be most deficient in the suppression of licking when shock
'This research was supported by PHS grants MH 26973 and S05 RR 7031 to Gabriel P. Frommer. A shorter version of this research was presented at the Society for Neuroscience meetings, 1977 [18].
Copyright ~ 1979 Brain R e s e a r c h Publications Inc.--0031-9384/79/010139-09502.00/0
141)
HOYMAN, WEESE AND FROMMER
predicting visual cues were presented in the visual field contralaterai to the lesion. However, other experiments [2,8] have shown that while rats were unable to perform a contraversive escape response in a T-maze, they were able to make full use of contralateral visual information if a forward-directed avoidance response was required. Since most of the above studies employed aversive shock, the present study sought to examine the effects of unilateral LH lesions on purely appetitive discrimination performance. Three different tactile discrimination tasks which differed in the spatial relations between the discriminative stimuli and the instrumental responses were used in an attempt to isolate operationally sensory and response processes. The effects of the lesions on these tasks were then compared to the effects of the same lesions on a battery of neurologic tests similar to those used in previous neglect studies. EXPERIMENT 1
In this experiment the effects of unilateral L H lesions were examined on an appetitive task in which 0.5 g touch stimuli were applied randomly to the right or left flank, and a correct response was a head-turn toward the same side as the touch. This task represented the control condition in which all relevant processes were confined to the same hemisphere on each trial. The rats were also tested on a neurologlc battery derived from that used by Marshall and co-workers to define the phenomenon of sensory neglect [21,22].
Method Animals. Five female Simonsen hooded rats weighing approximately 200 g at the time of surgery were trained and lesioned. The rats were doubly housed prior to surgery and singly housed tbercafter in an artificially lighted room which was darkened for 12 hr at night. During training and testing the rats were allowed 15 rain access to water after each d a y ' s session and had constant access to Purina rat chow. Apparatus. Discrimination training took place in a 17×9x I 1 cm clear plastic chamber, the sides of which had 10x8 cm holes interrupted by vertical plastic rods spaced 3 cm apart. The floor was made o f stainless steel rods spaced 2 cm apart. Thrt~ 1.3-cm dia. holes, one centered in the front walt 6 cm from the floor and one on each side wall 6 cm from the floor and 2 cm from the front wall. had photocells iVector VT241) and 28 V miniature lamps (No. 327) positioned to detect nose-poke responses. Behind each side hole was a drinking tube filled with 8% sucrose solution which was accessible only wben a circular aluminum door was rotated open by a 30 rev/min clock motor, A drinkometer circuit between the drinking tubes and the grid floor recorded licks on the tubes. Tactile stimuli were presented manually by the experimenter by means o f Von Frey hairs made of 0.15-ram dia. piano wires approximately 15 cm long. Each was ~ to a plastic handle and had a 2-ram dia. styrofoam bali cem4mted on the end. The force of each o f the hairs was calibrated by varying the length of the unattached wire until it bent at the desired force. During each exporin~ntal session the exl~rireenter sat with Von Frey hairs poised in both hands which were resting on soft pads situated at the level of the open sides of the chamber. Colored lights cued the experimenter to touch the rat's flank through the bars of the chamber on either the right or left side. BRS 200 series solid state pro-
gramming equipment controlled access to the drinking tubes. cued the experimenter to present stimuli, and recorded response events on both counters and a four channel paper tape event recorder. Stimulus presentations were made according to one of three semirandom sequences originally generated by a computer program using the rules set forth by Fellows [91 for minimizing nondiscriminative strategies such as position biases, alternation, and win-stay, lose-shift. The action of the event recorder and counters was delayed until after the rat made a response to prevent the tactile stimuli from being confounded with auditory cues. Surger3,. Prior to training each rat was implanted with a chronic unilateral electrode aimed at the LH which was later used to produce a lesion. Each rat received IP injections of 5 mg methylatropine followed by a mixture of pentobarbital, magnesium sulfate, and chloral hydrate (Equi-Thesin or Chlor-Pent, 2.5 ml/kg) to induce anesthesia. The rat was blinded by enucleation to prevent it from seeing the delivery of the touch in the task. Then the head was fixed in a stereotaxic instrument which positioned the top of the skull horizontally [121 and the skull was exposed and carefully cleaned and dried. After a thin layer of dental cement (Caulk, Grip, Ivory) was applied, a hole was drilled in the skull, and a single strand electrode of Teflon coated 0.17-ram dia. stainless steel with only the cross section exposed at the tip was implanted 3.0 mm caudal to bregma, 2.0ram lateral to the midline, and 7.6 mm below dura and was fixed to the skull with dental cement. Procedure. After recovering from the electrode implantation, each rat was adapted to having 15 rain access to water each day and was shaped to lick the 8% sucrose solution from each of the two drinking tubes. Usually, 15 min shaping for two or three days was sufficient to stabilize the licking rate but not sufficient to extinguish random nose-poke responses in the center hole in the front wall. Following shaping, the automated tactile discrimination program began, During initial training, each session continued until the rat had obtained 12 reinforcements on each tube (correction procedure). To initiate trials (stimulus presentations) the rat was required to make an observing response in the center hole following a period of 3 sec or longer with no responses in any of the three holes. Trials began with the experimenter briefly touching the rat's middle flank between the front and hind legs with a 0.5 g Von Frey hair on either the right or the left side. If the rat was touched on the right side and broke the photocell beam in the right hole within 5 sec, the tube access door opened for 5 sec (timed from the first tongue contact with the sucrose tube). Similarly, a touch on the left followed by a response to the left was rewarded with 5 sec of licking on the left tube. An error of omission was defined as a failure to respond in one of the side holes within 5 sec after the experimenter presented the touch stimulus (and simultaneously pressed a foot pedal which signaled to the program the moment o f presentation of the touch). Responding in the hole opposite to the touched flank within the 5-sec period w a s an error of commission. As the rats approached the baseline criterion of no more than one error per session for three consecutive days, a noncorrection procedure was initiated and continued for the duration of the experiment, whereby the rat was presented with exactly 24 trials each session. Immediately after achieving criterion each rat was anesthetized with ether, and 2.0 mA anodal current was passed through the implanted electrode for 20 sec. If no obvious symptoms of neglect appeared on
TACTILE DISCRIMINATION DEFICITS FOLLOWING LH LESIONS the neurologic tests on the subsequent day, a second identical amount of cmrent was pasted t h r o u ~ the electrode, and the rat was retested on the discrimination. After the usual twenty-four 0.5 g stimulus presentations of the session, the data were recorded, and several additional trials were run. An ascending series of touch intensities (1, 2, 4, 8, and 16 g) was presented on the side where errors, if any, had occurred until either a ~ response was made or the 16 g touch failed to produce a correct response. An additional test trial in which two 0.5 g touches were simultaneously presented on both sides was included if few errors occurred on either side during the initial 24 trials. The rat was tested in this fashion for four successive days after the lesion, and intermittently thereafter. Each rat underwent a battery of neuroiogic tests just before its di~'~rimination session on at least 3 occasions prior to the lesion and on testing days following the lesion. The rats were always tramported to the testing room in their home cages so that the orientation tests, which ware performed with the rat in its home cage, could be performed before handling the rat ou that day. We have found that the orienting response to a tactile stimulus is very reliable and brisk when teated in an enclosed space, especially the home cage. Testing on an open platform, as did Marshall and ¢,oworkers, requires extended "training," and responses under these conditions remain less vigorous and reliable in our hands. A small, soft paintbrush with a 20-cm long handle was used to test orienting to light tactile stimuli. By carefully and noiselessly moving the brush through the wire of the home cage the experimenter lightly touched the rat on either the snout, shoztMer area, lower foreleg, middle flank, rear flank, or lower hindiq. Orientation responses were judged as "strong" if the rat turned toward or bit the probe, as " w e a k " if any movement at all in the direction of the probe occurred, and as "absent" if no movement or movement away from the probe occurred. A 27x37 cm elliptical platform was used for observation of open field locomotor behavior. Besides noting general posture and the amount of locomotion, the experimenter kept a record of the number of tarns made to ceeh side during a l-rain period beginning when the rat was placed on the field. As a further test of body side preference the rat was suspended by the tail and the direction it twisted its body in climbing its tail was noted. Also, each rat was allowed to hang by its forepaws from a horizontal rod in order to note which paw released its grip first. These tests taken together served as the main criteria for determining the presence of the "sensory neglect" syndrome, although various other tests and observations were often made. Histology. After testing had been completed, the rats received an overdose of anesthetic and were perfused intracardially with isotonic saline followed by 10% formol--saline. The brains were extracted, and frozen slices 40 /~ thick were made through the extent of the lesions. The sections were mounted and stained with cresyl violet. Photographic prints were made of key sections on Kodabromide F-5 paper by using the stained section as a negative in a photographic enlarger. A No. 8k2 Wratten filter was used to remove the blue and violet wavelengths from the light source of the enlarger in order to prevent the violet of the stain from exposing the photographic paper and decreasing the contrast. Data analysis. Mean performance for all measures was defined as the mean for the 3 days preceding and the 3 days immediately following the lesion. The ITI responses were
141
obtained from a paper tape record and were manually tabulated with the provision that very rapid sequences of responses were not to he considered separate r e d s unless the white of the paper showed between the pen marks (requiring about 0.5 sec separation). Statistical analyses were made by means of matched group two tailed t-tests which simply compared the mean performance of each of the rats before the lesion to its mean performance after the lesion. Every t-test was made with 3 degrees of freedom since four rats always provided the final data.
Results and Discussion Anatomy. Figure 1 illustrates the lesions in the four rats which completed testing. They were all located in the caudal 2/3 of the lateral hypothalamus. Rats 2 and 3 displayed neuroioocal asymmetries foliowing a s i n l k stage lesion that damaged the lateral part of the LH, the medial ~ of the internal capsule, and the subea_Osular region. Of the remaining 2 rats requiring 2 stage lesions, Rat 1 sustained the most extensive damage involving virtually all of the LH, an approximately equal amount of the internal capsule, and a small amount of the subcapsular region. Rat 4 sustained damage to most of the LH, a lesser amount of the internal capsule, and most of the subcapsular region. A fifth rat with an even more extensive lesion showed signs of general debilitation and was dropped from further consideration because it made only a few observing responses in the task on the first three postlesion days. Neurologic tests. All 4 rats displayed a nearly total failure to orient toward light touches anywhere on the flank, snout, or legs on the side contralateral to the lesion. Prior to the lesion, 96% of all touches resulted in a response rated as "strong." Following the lesion, 100% of the touches to the ipsilateral side produced a "strong" response, while 2% of the touches to the contralateral side produced a "strong" response, 13% produced a " w e a k " response, and 85% resuRed in an "absent" rating. A notable exception to this trend occurred in the most severely affected animal, Rat I, on the fwst day following the lesion. This rat reliably responded to contralateral touches by circling away from the probe while at the same time displaying a violent enhanced responsiveness to ipsilateral touches. Occasional instances of increased biting and chasing of the probe seen in the remaining rats suggested that enhanced responsiveness ipsilateral to the lesion may have occurred to some extent in all of the rats. Asymmetries were also quite evident during open field locomotion. Preoperatively the rats made a mean of 6.2 contraversive turns and 6.3 ipsiversive turns in the first rain on the open field, while postoperatively only 2.3 contraversive turns and 11.0 ipsiversive turns were made. The other neurological tests produced the same general result, enhanced responsiveness ipsilaterai and decreased responsiveness contralateral to the lesion. Some grooming and locomotor responses were usually observed on the ipsilaterai side. Thus, our lesions in conjunction with our neurological tests produced results closely similar to those reported in previous studies [22] Tactile discrimination. The unilateral LH lesions produced a selective deficit on only half of the trials of the discrimination. The mean number of correct responses decreased significantly (p
